The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors
Abstract
:1. Overview on Ovarian cancer
2. OvCA Tumor Immune Microenvironment (TIME)
3. Macrophages
4. Neutrophils
5. γδ T Lymphocytes
6. Natural Killer cells
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ADCC | Antibody Dependent Cellular Cytotoxicity |
ARG | Arginase |
BM | Bone Marrow |
CAR-NK cells | Chimeric Antigen Receptor Natural Killer cells |
CB | Cord Blood cells |
CCL3/MIP-1α | Macrophage Inflammatory Protein-1α |
CSF | Colony Stimulator Factor |
CTLs | Cytotoxic T Cells |
DNAM-1 | DNAX Accessory Molecule-1 |
EGF | Epidermal Growth Factor |
EOC | Epithelial Ovarian Cancer |
FIGO | International Federation of Gynecology and Obstetrics |
GROα/β | Growth-Regulated Oncogeneα/β |
HB-EGF | Heparin-Binding EGF-like Growth Factor |
HGSOC | High-Grade Serous Ovarian Cancer |
HSCs | Hematopoietic Stem Cells |
Hu-mAb | Humanized monoclonal antibodies |
IFNγ | Interferon γ |
iNOS | Inducible Nitric Oxide Synthase |
iPSC | Induced Pluripotent Stem Cell |
LPS | Lipo Poly Saccharide |
MCP-1/CCL2 | Monocyte Chemoattractant Protein-1 |
M-CSF-1 | Macrophage Colony Stimulating Factor-1 |
mDAMPs | Mitochondrial Damage-Associated Molecular Patterns |
MDSCs | Myeloid Derived Suppressor Cells |
MIC A/B | MHC class I chain-related protein A and B |
MIF | Macrophage migration Inhibitory Factor |
MMPs | Matrix Metallo Proteinases |
N-BPs | Aminobisphosphonate |
NETs | Neutrophil Extracellular Traps |
NK | Natural Killer |
NKG2D | Natural Killer Group 2 member D |
NKG2DL | Natural Killer Group 2 member D Ligand |
NLR | Neutrophil–Lymphocyte Ratio |
OvCA | Ovarian Cancer |
PAD4 | Peptidyl Arginine Deiminase 4 |
PARP | Poly (Adenosine diphosphate-Ribose) Polymerase |
PB | Peripheral Blood cells |
PD-1 | Programmed cell Death-1 |
PD-L1 | Programmed cell Death Ligand-1 |
PFs | Peritoneal Fluids |
PlGF | Placental Growth Factor |
ROS | Reactive Oxygen Species |
SIRPα | Signal Regulatory Protein α |
TAM | Tumor-Associated Macrophages |
TANs | Tumor-Associated Neutrophils |
TME | Tumor Microenvironment |
TIME | Tumor Immune Microenvironment |
TGFβ | Transforming Growth Factor β |
TKIs | Tyrosine Kinase Inhibitors |
TNFα | Tumor Necrosis Factor α |
TSP-1 | ThromboSPondin-1 |
VEGF | Vascular Endothelial Growth Factor |
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin. 2019, 69, 7–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Momenimovahed, Z.; Tiznobaik, A.; Taheri, S.; Salehiniya, H. Ovarian cancer in the world: Epidemiology and risk factors. Int. J. Women’s Health 2019, 11, 287–299. [Google Scholar] [CrossRef] [Green Version]
- Bast, R.C., Jr.; Hennessy, B.; Mills, G.B. The biology of ovarian cancer: New opportunities for translation. Nat. Rev. Cancer 2009, 9, 415–428. [Google Scholar] [CrossRef] [PubMed]
- Koshiyama, M.; Matsumura, N.; Konishi, I. Subtypes of Ovarian Cancer and Ovarian Cancer Screening. Diagnostics (Basel) 2017, 7, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duska, L.R.; Kohn, E.C. The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications. Ann. Oncol. 2017, 28, viii8–viii12. [Google Scholar] [CrossRef] [PubMed]
- Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011, 474, 609–615. [Google Scholar] [CrossRef]
- Ignacio, R.M.C.; Lee, E.S.; Wilson, A.J.; Beeghly-Fadiel, A.; Whalen, M.M.; Son, D.S. Chemokine Network and Overall Survival in TP53 Wild-Type and Mutant Ovarian Cancer. Immune Netw. 2018, 18, e29. [Google Scholar] [CrossRef]
- Lynch, H.T.; Snyder, C.; Casey, M.J. Hereditary ovarian and breast cancer: What have we learned? Ann. Oncol. 2013, 24 (Suppl. S8), viii83–viii95. [Google Scholar] [CrossRef]
- Toss, A.; Tomasello, C.; Razzaboni, E.; Contu, G.; Grandi, G.; Cagnacci, A.; Schilder, R.J.; Cortesi, L. Hereditary ovarian cancer: Not only BRCA 1 and 2 genes. BioMed Res. Int. 2015, 2015, 341723. [Google Scholar] [CrossRef] [Green Version]
- Colombo, N.; Sessa, C.; du Bois, A.; Ledermann, J.; McCluggage, W.G.; McNeish, I.; Morice, P.; Pignata, S.; Ray-Coquard, I.; Vergote, I.; et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: Pathology and molecular biology, early and advanced stages, borderline tumours and recurrent diseasedagger. Ann. Oncol. 2019, 30, 672–705. [Google Scholar] [CrossRef] [Green Version]
- Tewari, K.S.; Burger, R.A.; Enserro, D.; Norquist, B.M.; Swisher, E.M.; Brady, M.F.; Bookman, M.A.; Fleming, G.F.; Huang, H.; Homesley, H.D.; et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J. Clin. Oncol. 2019, 37, 2317–2328. [Google Scholar] [CrossRef] [PubMed]
- Mendiola, M.; Redondo, A.; Heredia-Soto, V.; Herranz, J.; Berjon, A.; Hernandez, A.; Miguel-Martin, M.; Crespo, R.; Barriuso, J.; Cruz, P.; et al. Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes. Anticancer Res. 2018, 38, 5393–5400. [Google Scholar] [CrossRef] [PubMed]
- Binnewies, M.; Roberts, E.W.; Kersten, K.; Chan, V.; Fearon, D.F.; Merad, M.; Coussens, L.M.; Gabrilovich, D.I.; Ostrand-Rosenberg, S.; Hedrick, C.C.; et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018, 24, 541–550. [Google Scholar] [CrossRef] [PubMed]
- Balkwill, F.R.; Capasso, M.; Hagemann, T. The tumor microenvironment at a glance. J. Cell Sci. 2012, 125, 5591–5596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013, 19, 1423–1437. [Google Scholar] [CrossRef] [PubMed]
- Lengyel, E. Ovarian cancer development and metastasis. Am. J. Pathol. 2010, 177, 1053–1064. [Google Scholar] [CrossRef]
- Motohara, T.; Masuda, K.; Morotti, M.; Zheng, Y.; El-Sahhar, S.; Chong, K.Y.; Wietek, N.; Alsaadi, A.; Karaminejadranjbar, M.; Hu, Z.; et al. An evolving story of the metastatic voyage of ovarian cancer cells: Cellular and molecular orchestration of the adipose-rich metastatic microenvironment. Oncogene 2019, 38, 2885–2898. [Google Scholar] [CrossRef] [Green Version]
- Worzfeld, T.; Pogge von Strandmann, E.; Huber, M.; Adhikary, T.; Wagner, U.; Reinartz, S.; Muller, R. The Unique Molecular and Cellular Microenvironment of Ovarian Cancer. Front. Oncol. 2017, 7, 24. [Google Scholar] [CrossRef] [Green Version]
- Leinster, D.A.; Kulbe, H.; Everitt, G.; Thompson, R.; Perretti, M.; Gavins, F.N.; Cooper, D.; Gould, D.; Ennis, D.P.; Lockley, M.; et al. The peritoneal tumour microenvironment of high-grade serous ovarian cancer. J. Pathol. 2012, 227, 136–145. [Google Scholar] [CrossRef] [Green Version]
- Yang, Y. Cancer immunotherapy: Harnessing the immune system to battle cancer. J. Clin. Investig. 2015, 125, 3335–3337. [Google Scholar] [CrossRef] [Green Version]
- Curtis, M.; Mukherjee, A.; Lengyel, E. The Tumor Microenvironment Takes Center Stage in Ovarian Cancer Metastasis. Trends Cancer 2018, 4, 517–519. [Google Scholar] [CrossRef] [PubMed]
- Drakes, M.L.; Stiff, P.J. Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment. Cancers (Basel) 2018, 10, 302. [Google Scholar] [CrossRef] [Green Version]
- Hansen, J.M.; Coleman, R.L.; Sood, A.K. Targeting the tumour microenvironment in ovarian cancer. Eur. J. Cancer 2016, 56, 131–143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Okla, K.; Wertel, I.; Polak, G.; Surowka, J.; Wawruszak, A.; Kotarski, J. Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges. Int. Rev. Immunol. 2016, 35, 372–385. [Google Scholar] [CrossRef] [PubMed]
- Ou, Y.; Cannon, M.J.; Nakagawa, M. Regulatory T Cells in Gynecologic Cancer. MOJ Immunol. 2018, 6, 34–42. [Google Scholar] [CrossRef] [PubMed]
- Stenzel, A.E.; Abrams, S.I.; Moysich, K.B. A Call for Epidemiological Research on Myeloid-Derived Suppressor Cells in Ovarian Cancer: A Review of the Existing Immunological Evidence and Suggestions for Moving Forward. Front. Immunol. 2019, 10, 1608. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wen, Z.; Liu, H.; Li, M.; Li, B.; Gao, W.; Shao, Q.; Fan, B.; Zhao, F.; Wang, Q.; Xie, Q.; et al. Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration. Oncogene 2015, 34, 1241–1252. [Google Scholar] [CrossRef] [PubMed]
- Allavena, P.; Sica, A.; Solinas, G.; Porta, C.; Mantovani, A. The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages. Crit. Rev. Oncol. Hematol. 2008, 66, 1–9. [Google Scholar] [CrossRef]
- Pollard, J.W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 2004, 4, 71–78. [Google Scholar] [CrossRef]
- Yuan, X.; Zhang, J.; Li, D.; Mao, Y.; Mo, F.; Du, W.; Ma, X. Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta-analysis. Gynecol. Oncol. 2017, 147, 181–187. [Google Scholar] [CrossRef]
- Zhang, M.; He, Y.; Sun, X.; Li, Q.; Wang, W.; Zhao, A.; Di, W. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J. Ovarian Res. 2014, 7, 19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Q.W.; Liu, L.; Gong, C.Y.; Shi, H.S.; Zeng, Y.H.; Wang, X.Z.; Zhao, Y.W.; Wei, Y.Q. Prognostic significance of tumor-associated macrophages in solid tumor: A meta-analysis of the literature. PLoS ONE 2012, 7, e50946. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maccio, A.; Gramignano, G.; Cherchi, M.C.; Tanca, L.; Melis, L.; Madeddu, C. Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients. Sci. Rep. 2020, 10, 6096. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ciucci, A.; Zannoni, G.F.; Buttarelli, M.; Martinelli, E.; Mascilini, F.; Petrillo, M.; Ferrandina, G.; Scambia, G.; Gallo, D. Ovarian low and high grade serous carcinomas: Hidden divergent features in the tumor microenvironment. Oncotarget 2016, 7, 68033–68043. [Google Scholar] [CrossRef] [Green Version]
- Reinartz, S.; Schumann, T.; Finkernagel, F.; Wortmann, A.; Jansen, J.M.; Meissner, W.; Krause, M.; Schworer, A.M.; Wagner, U.; Muller-Brusselbach, S.; et al. Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse. Int. J. Cancer 2014, 134, 32–42. [Google Scholar] [CrossRef]
- Carroll, M.J.; Kapur, A.; Felder, M.; Patankar, M.S.; Kreeger, P.K. M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop. Oncotarget 2016, 7, 86608–86620. [Google Scholar] [CrossRef] [Green Version]
- Hagemann, T.; Wilson, J.; Kulbe, H.; Li, N.F.; Leinster, D.A.; Charles, K.; Klemm, F.; Pukrop, T.; Binder, C.; Balkwill, F.R. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J. Immunol. 2005, 175, 1197–1205. [Google Scholar] [CrossRef] [Green Version]
- Leber, T.M.; Balkwill, F.R. Regulation of monocyte MMP-9 production by TNF-alpha and a tumour-derived soluble factor (MMPSF). Br. J. Cancer 1998, 78, 724–732. [Google Scholar] [CrossRef] [Green Version]
- Hagemann, T.; Wilson, J.; Burke, F.; Kulbe, H.; Li, N.F.; Pluddemann, A.; Charles, K.; Gordon, S.; Balkwill, F.R. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol. 2006, 176, 5023–5032. [Google Scholar] [CrossRef] [Green Version]
- Neyen, C.; Pluddemann, A.; Mukhopadhyay, S.; Maniati, E.; Bossard, M.; Gordon, S.; Hagemann, T. Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer. J. Immunol. 2013, 190, 3798–3805. [Google Scholar] [CrossRef] [Green Version]
- Germano, G.; Frapolli, R.; Belgiovine, C.; Anselmo, A.; Pesce, S.; Liguori, M.; Erba, E.; Uboldi, S.; Zucchetti, M.; Pasqualini, F.; et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 2013, 23, 249–262. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Penn, C.A.; Yang, K.; Zong, H.; Lim, J.Y.; Cole, A.; Yang, D.; Baker, J.; Goonewardena, S.N.; Buckanovich, R.J. Therapeutic Impact of Nanoparticle Therapy Targeting Tumor-Associated Macrophages. Mol. Cancer Ther. 2018, 17, 96–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, X.; Meng, T. Depletion of tumor-associated macrophages enhances the anti-tumor effect of docetaxel in a murine epithelial ovarian cancer. Immunobiology 2019, 224, 355–361. [Google Scholar] [CrossRef] [PubMed]
- Moughon, D.L.; He, H.; Schokrpur, S.; Jiang, Z.K.; Yaqoob, M.; David, J.; Lin, C.; Iruela-Arispe, M.L.; Dorigo, O.; Wu, L. Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer. Cancer Res. 2015, 75, 4742–4752. [Google Scholar] [CrossRef] [Green Version]
- Jeong, M.; Kim, H.M.; Ahn, J.H.; Lee, K.T.; Jang, D.S.; Choi, J.H. 9-Hydroxycanthin-6-one isolated from stem bark of Ailanthus altissima induces ovarian cancer cell apoptosis and inhibits the activation of tumor-associated macrophages. Chem. Biol. Interact. 2018, 280, 99–108. [Google Scholar] [CrossRef]
- Wanderley, C.W.; Colon, D.F.; Luiz, J.P.M.; Oliveira, F.F.; Viacava, P.R.; Leite, C.A.; Pereira, J.A.; Silva, C.M.; Silva, C.R.; Silva, R.L.; et al. Paclitaxel Reduces Tumor Growth by Reprogramming Tumor-Associated Macrophages to an M1 Profile in a TLR4-Dependent Manner. Cancer Res. 2018, 78, 5891–5900. [Google Scholar] [CrossRef] [Green Version]
- Dangaj, D.; Abbott, K.L.; Mookerjee, A.; Zhao, A.; Kirby, P.S.; Sandaltzopoulos, R.; Powell, D.J., Jr.; Lamaziere, A.; Siegel, D.L.; Wolf, C.; et al. Mannose receptor (MR) engagement by mesothelin GPI anchor polarizes tumor-associated macrophages and is blocked by anti-MR human recombinant antibody. PLoS ONE 2011, 6, e28386. [Google Scholar] [CrossRef] [Green Version]
- Lee, K.; Ahn, J.H.; Lee, K.T.; Jang, D.S.; Choi, J.H. Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages. Nutrients 2018, 10, 91. [Google Scholar] [CrossRef] [Green Version]
- Keir, M.E.; Butte, M.J.; Freeman, G.J.; Sharpe, A.H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 2008, 26, 677–704. [Google Scholar] [CrossRef] [Green Version]
- Ren, J.; Zhu, X.; Xu, P.; Li, R.; Fu, Y.; Dong, S.; Zhangsun, D.; Wu, Y.; Luo, S. d-Amino Acid Substitution of alpha-Conotoxin RgIA Identifies its Critical Residues and Improves the Enzymatic Stability. Mar. Drugs 2019, 17, 142. [Google Scholar] [CrossRef] [Green Version]
- Gottlieb, C.E.; Mills, A.M.; Cross, J.V.; Ring, K.L. Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors. Gynecol. Oncol. 2017, 144, 607–612. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.H.; Choi, K.U.; Kim, A.; Lee, S.J.; Lee, J.H.; Suh, D.S.; Kwon, B.S.; Hwang, C. PD-L1 expression on stromal tumor-infiltrating lymphocytes is a favorable prognostic factor in ovarian serous carcinoma. J. Ovarian Res. 2019, 12, 56. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Zeng, B.; Zhang, Z.; Zhang, Y.; Yang, R. B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer. Clin. Immunol. 2008, 129, 471–481. [Google Scholar] [CrossRef] [PubMed]
- Kryczek, I.; Wei, S.; Zhu, G.; Myers, L.; Mottram, P.; Cheng, P.; Chen, L.; Coukos, G.; Zou, W. Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res. 2007, 67, 8900–8905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kryczek, I.; Zou, L.; Rodriguez, P.; Zhu, G.; Wei, S.; Mottram, P.; Brumlik, M.; Cheng, P.; Curiel, T.; Myers, L.; et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J. Exp. Med. 2006, 203, 871–881. [Google Scholar] [CrossRef] [PubMed]
- Barclay, A.N. Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function. Curr. Opin. Immunol. 2009, 21, 47–52. [Google Scholar] [CrossRef] [Green Version]
- Liu, R.; Wei, H.; Gao, P.; Yu, H.; Wang, K.; Fu, Z.; Ju, B.; Zhao, M.; Dong, S.; Li, Z.; et al. CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis. Oncotarget 2017, 8, 39021–39032. [Google Scholar] [CrossRef] [Green Version]
- McKinstry, W.J.; Li, C.L.; Rasko, J.E.; Nicola, N.A.; Johnson, G.R.; Metcalf, D. Cytokine receptor expression on hematopoietic stem and progenitor cells. Blood 1997, 89, 65–71. [Google Scholar] [CrossRef] [Green Version]
- Ng, L.G.; Ostuni, R.; Hidalgo, A. Heterogeneity of neutrophils. Nat. Rev. Immunol. 2019, 19, 255–265. [Google Scholar] [CrossRef]
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [Green Version]
- Coffelt, S.B.; Wellenstein, M.D.; de Visser, K.E. Neutrophils in cancer: Neutral no more. Nat. Rev. Cancer 2016, 16, 431–446. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Swierczak, A.; Mouchemore, K.A.; Hamilton, J.A.; Anderson, R.L. Neutrophils: Important contributors to tumor progression and metastasis. Cancer Metastasis Rev. 2015, 34, 735–751. [Google Scholar] [CrossRef] [PubMed]
- Fridlender, Z.G.; Albelda, S.M. Tumor-associated neutrophils: Friend or foe? Carcinogenesis 2012, 33, 949–955. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nozawa, H.; Chiu, C.; Hanahan, D. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc. Natl. Acad. Sci. USA 2006, 103, 12493–12498. [Google Scholar] [CrossRef] [Green Version]
- Powell, D.R.; Huttenlocher, A. Neutrophils in the Tumor Microenvironment. Trends Immunol. 2016, 37, 41–52. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fridlender, Z.G.; Sun, J.; Kim, S.; Kapoor, V.; Cheng, G.; Ling, L.; Worthen, G.S.; Albelda, S.M. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 2009, 16, 183–194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gentles, A.J.; Newman, A.M.; Liu, C.L.; Bratman, S.V.; Feng, W.; Kim, D.; Nair, V.S.; Xu, Y.; Khuong, A.; Hoang, C.D.; et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat. Med. 2015, 21, 938–945. [Google Scholar] [CrossRef]
- Jamieson, T.; Clarke, M.; Steele, C.W.; Samuel, M.S.; Neumann, J.; Jung, A.; Huels, D.; Olson, M.F.; Das, S.; Nibbs, R.J.; et al. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J. Clin. Investig. 2012, 122, 3127–3144. [Google Scholar] [CrossRef]
- Antonio, N.; Bonnelykke-Behrndtz, M.L.; Ward, L.C.; Collin, J.; Christensen, I.J.; Steiniche, T.; Schmidt, H.; Feng, Y.; Martin, P. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO J. 2015, 34, 2219–2236. [Google Scholar] [CrossRef]
- Shojaei, F.; Singh, M.; Thompson, J.D.; Ferrara, N. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc. Natl. Acad. Sci. USA 2008, 105, 2640–2645. [Google Scholar] [CrossRef] [Green Version]
- Spiegel, A.; Brooks, M.W.; Houshyar, S.; Reinhardt, F.; Ardolino, M.; Fessler, E.; Chen, M.B.; Krall, J.A.; DeCock, J.; Zervantonakis, I.K.; et al. Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells. Cancer Discov. 2016, 6, 630–649. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, Q.T.; Zhou, L.; Zeng, W.J.; Ma, Q.Q.; Wang, W.; Zhong, M.; Yu, Y.H. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Ovarian Cancer: A Systematic Review and Meta-Analysis of Observational Studies. Cell. Physiol. Biochem. 2017, 41, 2411–2418. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Q.; Hong, L.; Zuo, M.Z.; He, Z. Prognostic significance of neutrophil to lymphocyte ratio in ovarian cancer: Evidence from 4,910 patients. Oncotarget 2017, 8, 68938–68949. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Zhou, S.; Liu, Y.; Zhai, L.; Sun, X. Prognostic value of systemic inflammatory markers in ovarian Cancer: A PRISMA-compliant meta-analysis and systematic review. BMC Cancer 2018, 18, 443. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoshida, K.; Yoshikawa, N.; Shirakawa, A.; Niimi, K.; Suzuki, S.; Kajiyama, H.; Kikkawa, F. Prognostic value of neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma. J. Gynecol. Oncol. 2019, 30, e85. [Google Scholar] [CrossRef] [PubMed]
- Yeung, T.L.; Leung, C.S.; Wong, K.K.; Samimi, G.; Thompson, M.S.; Liu, J.; Zaid, T.M.; Ghosh, S.; Birrer, M.J.; Mok, S.C. TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 2013, 73, 5016–5028. [Google Scholar] [CrossRef] [Green Version]
- Mallmann-Gottschalk, N.; Sax, Y.; Kimmig, R.; Lang, S.; Brandau, S. EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells. Int. J. Mol. Sci. 2019, 20, 4693. [Google Scholar] [CrossRef] [Green Version]
- Lee, W.; Ko, S.Y.; Mohamed, M.S.; Kenny, H.A.; Lengyel, E.; Naora, H. Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J. Exp. Med. 2019, 216, 176–194. [Google Scholar] [CrossRef]
- Singel, K.L.; Grzankowski, K.S.; Khan, A.; Grimm, M.J.; D’Auria, A.C.; Morrell, K.; Eng, K.H.; Hylander, B.; Mayor, P.C.; Emmons, T.R.; et al. Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer. Br. J. Cancer 2019, 120, 207–217. [Google Scholar] [CrossRef] [Green Version]
- Shang, A.; Wang, W.; Gu, C.; Chen, C.; Zeng, B.; Yang, Y.; Ji, P.; Sun, J.; Wu, J.; Lu, W.; et al. Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils. J. Exp. Clin. Cancer Res. 2019, 38, 411. [Google Scholar] [CrossRef]
- Singel, K.L.; Emmons, T.R.; Khan, A.N.H.; Mayor, P.C.; Shen, S.; Wong, J.T.; Morrell, K.; Eng, K.H.; Mark, J.; Bankert, R.B.; et al. Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment. JCI Insight 2019, 4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aotsuka, A.; Matsumoto, Y.; Arimoto, T.; Kawata, A.; Ogishima, J.; Taguchi, A.; Tanikawa, M.; Sone, K.; Mori-Uchino, M.; Tsuruga, T.; et al. Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma. Cancer Sci. 2019, 110, 3068–3078. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rennard, S.I.; Dale, D.C.; Donohue, J.F.; Kanniess, F.; Magnussen, H.; Sutherland, E.R.; Watz, H.; Lu, S.; Stryszak, P.; Rosenberg, E.; et al. CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2015, 191, 1001–1011. [Google Scholar] [CrossRef] [PubMed]
- Cassier, P.A.; Italiano, A.; Gomez-Roca, C.A.; Le Tourneau, C.; Toulmonde, M.; Cannarile, M.A.; Ries, C.; Brillouet, A.; Muller, C.; Jegg, A.M.; et al. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: A dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015, 16, 949–956. [Google Scholar] [CrossRef]
- Ries, C.H.; Cannarile, M.A.; Hoves, S.; Benz, J.; Wartha, K.; Runza, V.; Rey-Giraud, F.; Pradel, L.P.; Feuerhake, F.; Klaman, I.; et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 2014, 25, 846–859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yung, M.M.; Tang, H.W.; Cai, P.C.; Leung, T.H.; Ngu, S.F.; Chan, K.K.; Xu, D.; Yang, H.; Ngan, H.Y.; Chan, D.W. GRO-alpha and IL-8 enhance ovarian cancer metastatic potential via the CXCR2-mediated TAK1/NFkappaB signaling cascade. Theranostics 2018, 8, 1270–1285. [Google Scholar] [CrossRef]
- Steele, C.W.; Karim, S.A.; Leach, J.D.G.; Bailey, P.; Upstill-Goddard, R.; Rishi, L.; Foth, M.; Bryson, S.; McDaid, K.; Wilson, Z.; et al. CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell 2016, 29, 832–845. [Google Scholar] [CrossRef] [Green Version]
- Benevides, L.; da Fonseca, D.M.; Donate, P.B.; Tiezzi, D.G.; De Carvalho, D.D.; de Andrade, J.M.; Martins, G.A.; Silva, J.S. IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment. Cancer Res. 2015, 75, 3788–3799. [Google Scholar] [CrossRef] [Green Version]
- Coffelt, S.B.; Kersten, K.; Doornebal, C.W.; Weiden, J.; Vrijland, K.; Hau, C.S.; Verstegen, N.J.M.; Ciampricotti, M.; Hawinkels, L.; Jonkers, J.; et al. IL-17-producing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis. Nature 2015, 522, 345–348. [Google Scholar] [CrossRef]
- Stark, M.A.; Huo, Y.; Burcin, T.L.; Morris, M.A.; Olson, T.S.; Ley, K. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 2005, 22, 285–294. [Google Scholar] [CrossRef] [Green Version]
- Highfill, S.L.; Cui, Y.; Giles, A.J.; Smith, J.P.; Zhang, H.; Morse, E.; Kaplan, R.N.; Mackall, C.L. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci. Transl. Med. 2014, 6, 237ra267. [Google Scholar] [CrossRef] [PubMed]
- Chung, A.S.; Wu, X.; Zhuang, G.; Ngu, H.; Kasman, I.; Zhang, J.; Vernes, J.M.; Jiang, Z.; Meng, Y.G.; Peale, F.V.; et al. An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nat. Med. 2013, 19, 1114–1123. [Google Scholar] [CrossRef] [PubMed]
- Farolfi, A.; Petrone, M.; Scarpi, E.; Galla, V.; Greco, F.; Casanova, C.; Longo, L.; Cormio, G.; Orditura, M.; Bologna, A.; et al. Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24). Target. Oncol. 2018, 13, 469–479. [Google Scholar] [CrossRef]
- Bhat, J.; Kabelitz, D. gammadelta T cells and epigenetic drugs: A useful merger in cancer immunotherapy? Oncoimmunology 2015, 4, e1006088. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bonneville, M.; O’Brien, R.L.; Born, W.K. Gammadelta T cell effector functions: A blend of innate programming and acquired plasticity. Nat. Rev. Immunol. 2010, 10, 467–478. [Google Scholar] [CrossRef] [PubMed]
- Fan, C.A.; Reader, J.; Roque, D.M. Review of Immune Therapies Targeting Ovarian Cancer. Curr. Treat. Options Oncol. 2018, 19, 74. [Google Scholar] [CrossRef] [PubMed]
- Poggi, A.; Zocchi, M.R. gammadelta T Lymphocytes as a First Line of Immune Defense: Old and New Ways of Antigen Recognition and Implications for Cancer Immunotherapy. Front. Immunol. 2014, 5, 575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carlsten, M.; Bjorkstrom, N.K.; Norell, H.; Bryceson, Y.; van Hall, T.; Baumann, B.C.; Hanson, M.; Schedvins, K.; Kiessling, R.; Ljunggren, H.G.; et al. DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. Cancer Res. 2007, 67, 1317–1325. [Google Scholar] [CrossRef] [Green Version]
- Guillamon, C.F.; Martinez-Sanchez, M.V.; Gimeno, L.; Mrowiec, A.; Martinez-Garcia, J.; Server-Pastor, G.; Martinez-Escribano, J.; Torroba, A.; Ferri, B.; Abellan, D.; et al. NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome. Cancer Immunol. Res. 2018, 6, 1537–1547. [Google Scholar] [CrossRef] [Green Version]
- McGilvray, R.W.; Eagle, R.A.; Rolland, P.; Jafferji, I.; Trowsdale, J.; Durrant, L.G. ULBP2 and RAET1E NKG2D ligands are independent predictors of poor prognosis in ovarian cancer patients. Int. J. Cancer 2010, 127, 1412–1420. [Google Scholar] [CrossRef]
- Wu, J.D.; Higgins, L.M.; Steinle, A.; Cosman, D.; Haugk, K.; Plymate, S.R. Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J. Clin. Investig. 2004, 114, 560–568. [Google Scholar] [CrossRef] [PubMed]
- Li, K.; Mandai, M.; Hamanishi, J.; Matsumura, N.; Suzuki, A.; Yagi, H.; Yamaguchi, K.; Baba, T.; Fujii, S.; Konishi, I. Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: High expression of ULBP2 is an indicator of poor prognosis. Cancer Immunol. Immunother. 2009, 58, 641–652. [Google Scholar] [CrossRef] [PubMed]
- Cai, X.; Caballero-Benitez, A.; Gewe, M.M.; Jenkins, I.C.; Drescher, C.W.; Strong, R.K.; Spies, T.; Groh, V. Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells. Neoplasia 2017, 19, 471–482. [Google Scholar] [CrossRef] [PubMed]
- Groh, V.; Wu, J.; Yee, C.; Spies, T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002, 419, 734–738. [Google Scholar] [CrossRef] [PubMed]
- Benitez, A.C.; Dai, Z.; Mann, H.H.; Reeves, R.S.; Margineantu, D.H.; Gooley, T.A.; Groh, V.; Spies, T. Expression, signaling proficiency, and stimulatory function of the NKG2D lymphocyte receptor in human cancer cells. Proc. Natl. Acad. Sci. USA 2011, 108, 4081–4086. [Google Scholar] [CrossRef] [Green Version]
- Cai, X.; Dai, Z.; Reeves, R.S.; Caballero-Benitez, A.; Duran, K.L.; Delrow, J.J.; Porter, P.L.; Spies, T.; Groh, V. Autonomous stimulation of cancer cell plasticity by the human NKG2D lymphocyte receptor coexpressed with its ligands on cancer cells. PLoS ONE 2014, 9, e108942. [Google Scholar] [CrossRef]
- Cua, S.; Tan, H.L.; Fong, W.J.; Chin, A.; Lau, A.; Ding, V.; Song, Z.; Yang, Y.; Choo, A. Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448. Oncotarget 2018, 9, 13206–13221. [Google Scholar] [CrossRef] [Green Version]
- Oberg, H.H.; Kellner, C.; Gonnermann, D.; Sebens, S.; Bauerschlag, D.; Gramatzki, M.; Kabelitz, D.; Peipp, M.; Wesch, D. Tribody [(HER2)2xCD16] Is More Effective Than Trastuzumab in Enhancing gammadelta T Cell and Natural Killer Cell Cytotoxicity Against HER2-Expressing Cancer Cells. Front. Immunol. 2018, 9, 814. [Google Scholar] [CrossRef]
- Silva-Santos, B.; Serre, K.; Norell, H. gammadelta T cells in cancer. Nat. Rev. Immunol. 2015, 15, 683–691. [Google Scholar] [CrossRef]
- Suto, A.; Kudo, D.; Yoshida, E.; Nagase, H.; Suto, S.; Mimura, J.; Itoh, K.; Hakamada, K. Increase of Tumor Infiltrating gammadelta T-cells in Pancreatic Ductal Adenocarcinoma Through Remodeling of the Extracellular Matrix by a Hyaluronan Synthesis Suppressor, 4-Methylumbelliferone. Pancreas 2019, 48, 292–298. [Google Scholar] [CrossRef]
- Ye, J.; Ma, C.; Wang, F.; Hsueh, E.C.; Toth, K.; Huang, Y.; Mo, W.; Liu, S.; Han, B.; Varvares, M.A.; et al. Specific recruitment of gammadelta regulatory T cells in human breast cancer. Cancer Res. 2013, 73, 6137–6148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, Y.; Niu, C.; Cui, J. Gamma-delta (gammadelta) T cells: Friend or foe in cancer development? J. Transl. Med. 2018, 16, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, X.; Shang, W.; Xu, R.; Wu, M.; Zhang, X.; Huang, P.; Wang, F.; Pan, S. Distribution and functions of gammadelta T cells infiltrated in the ovarian cancer microenvironment. J. Transl. Med. 2019, 17, 144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mao, T.L.; Miao, C.H.; Liao, Y.J.; Chen, Y.J.; Yeh, C.Y.; Liu, C.L. Ex Vivo Expanded Human Vgamma9Vdelta2 T-Cells Can Suppress Epithelial Ovarian Cancer Cell Growth. Int. J. Mol. Sci. 2019, 20, 1139. [Google Scholar] [CrossRef] [Green Version]
- Coukos, G.; Tanyi, J.; Kandalaft, L.E. Opportunities in immunotherapy of ovarian cancer. Ann. Oncol. 2016, 27 (Suppl. S1), i11–i15. [Google Scholar] [CrossRef] [Green Version]
- Parente-Pereira, A.C.; Shmeeda, H.; Whilding, L.M.; Zambirinis, C.P.; Foster, J.; van der Stegen, S.J.; Beatson, R.; Zabinski, T.; Brewig, N.; Sosabowski, J.K.; et al. Adoptive immunotherapy of epithelial ovarian cancer with Vgamma9Vdelta2 T cells, potentiated by liposomal alendronic acid. J. Immunol. 2014, 193, 5557–5566. [Google Scholar] [CrossRef] [Green Version]
- Becknell, B.; Caligiuri, M.A. Natural killer cells in innate immunity and cancer. J. Immunother. 2008, 31, 685–692. [Google Scholar] [CrossRef]
- Cooper, M.A.; Fehniger, T.A.; Caligiuri, M.A. The biology of human natural killer-cell subsets. Trends Immunol. 2001, 22, 633–640. [Google Scholar] [CrossRef]
- Vivier, E.; Tomasello, E.; Baratin, M.; Walzer, T.; Ugolini, S. Functions of natural killer cells. Nat. Immunol. 2008, 9, 503–510. [Google Scholar] [CrossRef]
- Albini, A.; Bruno, A.; Noonan, D.M.; Mortara, L. Contribution to Tumor Angiogenesis from Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy. Front. Immunol. 2018, 9, 527. [Google Scholar] [CrossRef]
- Bassani, B.; Baci, D.; Gallazzi, M.; Poggi, A.; Bruno, A.; Mortara, L. Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects. Cancers (Basel) 2019, 11, 461. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fogel, L.A.; Yokoyama, W.M.; French, A.R. Natural killer cells in human autoimmune disorders. Arthritis Res. Ther. 2013, 15, 216. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mandal, A.; Viswanathan, C. Natural killer cells: In health and disease. Hematol. Oncol. Stem Cell Ther. 2015, 8, 47–55. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parisi, L.; Bassani, B.; Tremolati, M.; Gini, E.; Farronato, G.; Bruno, A. Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases. J. Immunol. Res. 2017, 2017, 4218254. [Google Scholar] [CrossRef]
- Tian, Z.; Chen, Y.; Gao, B. Natural killer cells in liver disease. Hepatology 2013, 57, 1654–1662. [Google Scholar] [CrossRef]
- Bosi, A.; Zanellato, S.; Bassani, B.; Albini, A.; Musco, A.; Cattoni, M.; Desio, M.; Nardecchia, E.; D’Urso, D.G.; Imperatori, A.; et al. Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization. J. Immunol. Res. 2018, 2018, 2438598. [Google Scholar] [CrossRef] [Green Version]
- Bruno, A.; Bassani, B.; D’Urso, D.G.; Pitaku, I.; Cassinotti, E.; Pelosi, G.; Boni, L.; Dominioni, L.; Noonan, D.M.; Mortara, L.; et al. Angiogenin and the MMP9-TIMP2 axis are up-regulated in proangiogenic, decidual NK-like cells from patients with colorectal cancer. FASEB J. 2018. [Google Scholar] [CrossRef] [Green Version]
- Bruno, A.; Ferlazzo, G.; Albini, A.; Noonan, D.M. A think tank of TINK/TANKs: Tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis. J. Natl. Cancer Inst. 2014, 106, dju200. [Google Scholar] [CrossRef] [Green Version]
- Bruno, A.; Pagani, A.; Pulze, L.; Albini, A.; Dallaglio, K.; Noonan, D.M.; Mortara, L. Orchestration of angiogenesis by immune cells. Front. Oncol. 2014, 4, 131. [Google Scholar] [CrossRef]
- Carrega, P.; Morandi, B.; Costa, R.; Frumento, G.; Forte, G.; Altavilla, G.; Ratto, G.B.; Mingari, M.C.; Moretta, L.; Ferlazzo, G. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer 2008, 112, 863–875. [Google Scholar] [CrossRef]
- Lopez-Soto, A.; Gonzalez, S.; Smyth, M.J.; Galluzzi, L. Control of Metastasis by NK Cells. Cancer Cell 2017, 32, 135–154. [Google Scholar] [CrossRef] [PubMed]
- Poznanski, S.M.; Nham, T.; Chew, M.V.; Lee, A.J.; Hammill, J.A.; Fan, I.Y.; Butcher, M.; Bramson, J.L.; Lee, D.A.; Hirte, H.W.; et al. Expanded CD56(superbright)CD16(+) NK Cells from Ovarian Cancer Patients Are Cytotoxic against Autologous Tumor in a Patient-Derived Xenograft Murine Model. Cancer Immunol. Res. 2018, 6, 1174–1185. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodriguez, G.M.; Galpin, K.J.C.; McCloskey, C.W.; Vanderhyden, B.C. The Tumor Microenvironment of Epithelial Ovarian Cancer and Its Influence on Response to Immunotherapy. Cancers (Basel) 2018, 10, 242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, Y.; Yao, Z.; Zhao, Z.; Xiao, H.; Xia, M.; Zhu, X.; Jiang, X.; Sun, C. Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer. Exp. Ther. Med. 2018, 16, 1071–1078. [Google Scholar] [CrossRef]
- Gavalas, N.G.; Karadimou, A.; Dimopoulos, M.A.; Bamias, A. Immune response in ovarian cancer: How is the immune system involved in prognosis and therapy: Potential for treatment utilization. Clin. Dev. Immunol. 2010, 2010, 791603. [Google Scholar] [CrossRef] [Green Version]
- Patankar, M.S.; Jing, Y.; Morrison, J.C.; Belisle, J.A.; Lattanzio, F.A.; Deng, Y.; Wong, N.K.; Morris, H.R.; Dell, A.; Clark, G.F. Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125. Gynecol. Oncol. 2005, 99, 704–713. [Google Scholar] [CrossRef]
- Baert, T.; Vankerckhoven, A.; Riva, M.; Van Hoylandt, A.; Thirion, G.; Holger, G.; Mathivet, T.; Vergote, I.; Coosemans, A. Myeloid Derived Suppressor Cells: Key Drivers of Immunosuppression in Ovarian Cancer. Front. Immunol. 2019, 10, 1273. [Google Scholar] [CrossRef]
- Bruno, A.; Mortara, L.; Baci, D.; Noonan, D.M.; Albini, A. Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression. Front. Immunol. 2019, 10, 771. [Google Scholar] [CrossRef]
- Barnett, B.; Kryczek, I.; Cheng, P.; Zou, W.; Curiel, T.J. Regulatory T cells in ovarian cancer: Biology and therapeutic potential. Am. J. Reprod. Immunol. 2005, 54, 369–377. [Google Scholar] [CrossRef]
- Toker, A.; Nguyen, L.T.; Stone, S.C.; Yang, S.Y.C.; Katz, S.R.; Shaw, P.A.; Clarke, B.A.; Ghazarian, D.; Al-Habeeb, A.; Easson, A.; et al. Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma. Clin. Cancer Res. 2018, 24, 5685–5696. [Google Scholar] [CrossRef] [Green Version]
- Alsina-Sanchis, E.; Figueras, A.; Lahiguera, A.; Gil-Martin, M.; Pardo, B.; Piulats, J.M.; Marti, L.; Ponce, J.; Matias-Guiu, X.; Vidal, A.; et al. TGFbeta Controls Ovarian Cancer Cell Proliferation. Int. J. Mol. Sci. 2017, 18, 1658. [Google Scholar] [CrossRef] [PubMed]
- Alsina-Sanchis, E.; Figueras, A.; Lahiguera, A.; Vidal, A.; Casanovas, O.; Graupera, M.; Villanueva, A.; Vinals, F. The TGFbeta pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels. Int. J. Cancer 2016, 139, 1894–1903. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pickup, M.; Novitskiy, S.; Moses, H.L. The roles of TGFbeta in the tumour microenvironment. Nat. Rev. Cancer 2013, 13, 788–799. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loffek, S. Transforming of the Tumor Microenvironment: Implications for TGF-beta Inhibition in the Context of Immune-Checkpoint Therapy. J. Oncol. 2018, 2018, 9732939. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, X.; Li, X.; Wang, X.; Zhu, Q.; Wu, X.; Wang, X. MUC16 impacts tumor proliferation and migration through cytoplasmic translocation of P120-catenin in epithelial ovarian cancer cells: An original research. BMC Cancer 2019, 19, 171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Felder, M.; Kapur, A.; Gonzalez-Bosquet, J.; Horibata, S.; Heintz, J.; Albrecht, R.; Fass, L.; Kaur, J.; Hu, K.; Shojaei, H.; et al. MUC16 (CA125): Tumor biomarker to cancer therapy, a work in progress. Mol. Cancer 2014, 13, 129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duffy, M.J.; Bonfrer, J.M.; Kulpa, J.; Rustin, G.J.; Soletormos, G.; Torre, G.C.; Tuxen, M.K.; Zwirner, M. CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use. Int. J. Gynecol. Cancer 2005, 15, 679–691. [Google Scholar] [CrossRef]
- Sturgeon, C.M.; Duffy, M.J.; Stenman, U.H.; Lilja, H.; Brunner, N.; Chan, D.W.; Babaian, R.; Bast, R.C., Jr.; Dowell, B.; Esteva, F.J.; et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin. Chem. 2008, 54, e11–e79. [Google Scholar] [CrossRef] [Green Version]
- Gubbels, J.A.; Belisle, J.; Onda, M.; Rancourt, C.; Migneault, M.; Ho, M.; Bera, T.K.; Connor, J.; Sathyanarayana, B.K.; Lee, B.; et al. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol. Cancer 2006, 5, 50. [Google Scholar] [CrossRef] [Green Version]
- Harlozinska, A.; Sedlaczek, P.; Van Dalen, A.; Rozdolski, K.; Einarsson, R. TPS and CA 125 levels in serum, cyst fluid and ascites of patients with epithelial ovarian neoplasms. Anticancer Res. 1997, 17, 4473–4478. [Google Scholar]
- Lai, P.; Rabinowich, H.; Crowley-Nowick, P.A.; Bell, M.C.; Mantovani, G.; Whiteside, T.L. Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma. Clin. Cancer Res. 1996, 2, 161–173. [Google Scholar] [PubMed]
- Felder, M.; Kapur, A.; Rakhmilevich, A.L.; Qu, X.; Sondel, P.M.; Gillies, S.D.; Connor, J.; Patankar, M.S. MUC16 suppresses human and murine innate immune responses. Gynecol. Oncol. 2019, 152, 618–628. [Google Scholar] [CrossRef] [PubMed]
- Tyler, C.; Kapur, A.; Felder, M.; Belisle, J.A.; Trautman, C.; Gubbels, J.A.; Connor, J.P.; Patankar, M.S. The mucin MUC16 (CA125) binds to NK cells and monocytes from peripheral blood of women with healthy pregnancy and preeclampsia. Am. J. Reprod. Immunol. 2012, 68, 28–37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mills, G.B.; May, C.; Hill, M.; Campbell, S.; Shaw, P.; Marks, A. Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. J. Clin. Investig. 1990, 86, 851–855. [Google Scholar] [CrossRef] [Green Version]
- Mills, G.B.; May, C.; McGill, M.; Roifman, C.M.; Mellors, A. A putative new growth factor in ascitic fluid from ovarian cancer patients: Identification, characterization, and mechanism of action. Cancer Res. 1988, 48, 1066–1071. [Google Scholar]
- Pesce, S.; Tabellini, G.; Cantoni, C.; Patrizi, O.; Coltrini, D.; Rampinelli, F.; Matta, J.; Vivier, E.; Moretta, A.; Parolini, S.; et al. B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape. Oncoimmunology 2015, 4, e1001224. [Google Scholar] [CrossRef] [Green Version]
- Allan, D.S.; Rybalov, B.; Awong, G.; Zuniga-Pflucker, J.C.; Kopcow, H.D.; Carlyle, J.R.; Strominger, J.L. TGF-beta affects development and differentiation of human natural killer cell subsets. Eur. J. Immunol. 2010, 40, 2289–2295. [Google Scholar] [CrossRef] [Green Version]
- Cerdeira, A.S.; Rajakumar, A.; Royle, C.M.; Lo, A.; Husain, Z.; Thadhani, R.I.; Sukhatme, V.P.; Karumanchi, S.A.; Kopcow, H.D. Conversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors. J. Immunol. 2013, 190, 3939–3948. [Google Scholar] [CrossRef]
- Recchia, F.; Di Orio, F.; Candeloro, G.; Guerriero, G.; Piazze, J.; Rea, S. Maintenance immunotherapy in recurrent ovarian cancer: Long term follow-up of a phase II study. Gynecol. Oncol. 2010, 116, 202–207. [Google Scholar] [CrossRef]
- Medler, T.R.; Cotechini, T.; Coussens, L.M. Immune response to cancer therapy: Mounting an effective antitumor response and mechanisms of resistance. Trends Cancer 2015, 1, 66–75. [Google Scholar] [CrossRef] [Green Version]
- Zitvogel, L.; Kepp, O.; Kroemer, G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat. Rev. Clin. Oncol. 2011, 8, 151–160. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Ai, X.; Wu, C.; Wang, H.; Zeng, G.; Yang, P.; Liu, G. A novel human IL-2 mutein with minimal systemic toxicity exerts greater antitumor efficacy than wild-type IL-2. Cell Death Dis. 2018, 9, 989. [Google Scholar] [CrossRef] [PubMed]
- Mortara, L.; Balza, E.; Bruno, A.; Poggi, A.; Orecchia, P.; Carnemolla, B. Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy. Front. Immunol. 2018, 9, 2905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, Z.; Ren, Z.; Yang, K.; Liu, Z.; Cao, S.; Deng, S.; Xu, L.; Liang, Y.; Guo, J.; Bian, Y.; et al. A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8(+) T-cell response and effective tumor control. Nat. Commun. 2019, 10, 3874. [Google Scholar] [CrossRef]
- Wang, Y.; Zhang, Y.; Yi, P.; Dong, W.; Nalin, A.P.; Zhang, J.; Zhu, Z.; Chen, L.; Benson, D.M.; Mundy-Bosse, B.L.; et al. The IL-15-AKT-XBP1s signaling pathway contributes to effector functions and survival in human NK cells. Nat. Immunol. 2019, 20, 10–17. [Google Scholar] [CrossRef]
- Robinson, T.O.; Schluns, K.S. The potential and promise of IL-15 in immuno-oncogenic therapies. Immunol. Lett. 2017, 190, 159–168. [Google Scholar] [CrossRef]
- Leclercq, G.; Debacker, V.; de Smedt, M.; Plum, J. Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. J. Exp. Med. 1996, 184, 325–336. [Google Scholar] [CrossRef] [Green Version]
- Guo, Y.; Luan, L.; Patil, N.K.; Wang, J.; Bohannon, J.K.; Rabacal, W.; Fensterheim, B.A.; Hernandez, A.; Sherwood, E.R. IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function. J. Immunol. 2017, 198, 1320–1333. [Google Scholar] [CrossRef] [Green Version]
- Childs, R.W.; Carlsten, M. Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: The force awakens. Nat. Rev. Drug Discov. 2015, 14, 487–498. [Google Scholar] [CrossRef]
- Felices, M.; Chu, S.; Kodal, B.; Bendzick, L.; Ryan, C.; Lenvik, A.J.; Boylan, K.L.M.; Wong, H.C.; Skubitz, A.P.N.; Miller, J.S.; et al. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Gynecol. Oncol. 2017, 145, 453–461. [Google Scholar] [CrossRef]
- Hoogstad-van Evert, J.S.; Maas, R.J.; van der Meer, J.; Cany, J.; van der Steen, S.; Jansen, J.H.; Miller, J.S.; Bekkers, R.; Hobo, W.; Massuger, L.; et al. Peritoneal NK cells are responsive to IL-15 and percentages are correlated with outcome in advanced ovarian cancer patients. Oncotarget 2018, 9, 34810–34820. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, K.; Han, Y.; Cho, W.C.; Zhu, H. The rise of human stem cell-derived natural killer cells for cancer immunotherapy. Expert Opin. Biol. Ther. 2019, 19, 141–148. [Google Scholar] [CrossRef] [PubMed]
- Zeng, J.; Tang, S.Y.; Toh, L.L.; Wang, S. Generation of “Off-the-Shelf” Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells. Stem Cell Rep. 2017, 9, 1796–1812. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shimasaki, N.; Jain, A.; Campana, D. NK cells for cancer immunotherapy. Nat. Rev. Drug Discov. 2020. [Google Scholar] [CrossRef]
- Li, Y.; Hermanson, D.L.; Moriarity, B.S.; Kaufman, D.S. Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Cell Stem Cell 2018, 23, 181–192. [Google Scholar] [CrossRef] [Green Version]
- Abate-Daga, D.; Davila, M.L. CAR models: Next-generation CAR modifications for enhanced T-cell function. Mol. Ther. Oncolytics 2016, 3, 16014. [Google Scholar] [CrossRef] [Green Version]
- Li, D.; Li, X.; Zhou, W.L.; Huang, Y.; Liang, X.; Jiang, L.; Yang, X.; Sun, J.; Li, Z.; Han, W.D.; et al. Genetically engineered T cells for cancer immunotherapy. Signal. Transduct. Target. Ther. 2019, 4, 35. [Google Scholar] [CrossRef]
- Tokarew, N.; Ogonek, J.; Endres, S.; von Bergwelt-Baildon, M.; Kobold, S. Teaching an old dog new tricks: Next-generation CAR T cells. Br. J. Cancer 2019, 120, 26–37. [Google Scholar] [CrossRef] [Green Version]
- Leslie, M. New cancer-fighting cells enter trials. Science 2018, 361, 1056–1057. [Google Scholar] [CrossRef]
- Morvan, M.G.; Lanier, L.L. NK cells and cancer: You can teach innate cells new tricks. Nat. Rev. Cancer 2016, 16, 7–19. [Google Scholar] [CrossRef]
- Maliar, A.; Servais, C.; Waks, T.; Chmielewski, M.; Lavy, R.; Altevogt, P.; Abken, H.; Eshhar, Z. Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice. Gastroenterology 2012, 143, 1375–1384. [Google Scholar] [CrossRef] [PubMed]
- Salnikov, A.V.; Bretz, N.P.; Perne, C.; Hazin, J.; Keller, S.; Fogel, M.; Herr, I.; Schlange, T.; Moldenhauer, G.; Altevogt, P. Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas. Br. J. Cancer 2013, 108, 1449–1459. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, F.; Wang, T.; Jiang, J.; Wang, Y.; Ma, Z.; Li, Z.; Han, Y.; Pan, M.; Cai, J.; Wang, M.; et al. Engineering a high-affinity humanized anti-CD24 antibody to target hepatocellular carcinoma by a novel CDR grafting design. Oncotarget 2017, 8, 51238–51252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klapdor, R.; Wang, S.; Morgan, M.; Dork, T.; Hacker, U.; Hillemanns, P.; Buning, H.; Schambach, A. Characterization of a Novel Third-Generation Anti-CD24-CAR against Ovarian Cancer. Int. J. Mol. Sci. 2019, 20, 660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Baci, D.; Bosi, A.; Gallazzi, M.; Rizzi, M.; Noonan, D.M.; Poggi, A.; Bruno, A.; Mortara, L. The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors. Int. J. Mol. Sci. 2020, 21, 3125. https://doi.org/10.3390/ijms21093125
Baci D, Bosi A, Gallazzi M, Rizzi M, Noonan DM, Poggi A, Bruno A, Mortara L. The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors. International Journal of Molecular Sciences. 2020; 21(9):3125. https://doi.org/10.3390/ijms21093125
Chicago/Turabian StyleBaci, Denisa, Annalisa Bosi, Matteo Gallazzi, Manuela Rizzi, Douglas M. Noonan, Alessandro Poggi, Antonino Bruno, and Lorenzo Mortara. 2020. "The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors" International Journal of Molecular Sciences 21, no. 9: 3125. https://doi.org/10.3390/ijms21093125