Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Mechanisms of Immune Escape in HNSCC
2.1. Composition and Activation Profile of Immune Cells in the TME
2.2. Development of a Tumor-Promoting Microenvironment
2.3. Galectin-1 as a Soluble Immune Checkpoint
2.4. Alteration in the Antigen Presentation Machinery (APM)
3. Immune Checkpoint Pathways Implicated in HNSCC
3.1. CTLA-4
3.2. PD-1/PD-L1
3.3. LAG-3
3.4. TIM-3
3.5. TIGIT
4. Immune Checkpoint Blockade (ICB) in HNSCC Treatment
4.1. Combination of ICB with Other Therapies
4.2. Combination of ICB with Other Immunotherapies
4.3. ICB in the Neoadjuvant Setting
5. Biomarkers of Response to Immunotherapy in HNSCC
5.1. Tumor Genomic Features: Microsatellite Instability and Tumor Mutational Burden
5.2. Tobacco Smoke and HPV Status
5.3. PD-L1 Expression
5.4. T-Cell Inflamed Gene Expression and Novel Insights into the TME
5.5. Microbiota as a Potential Novel Biomarker of Response to Immunotherapy
5.6. Novel Insights in Biomarkers: Combined and Integrative Strategies
6. Conclusions and Future Directions
Funding
Acknowledgments
Conflicts of Interest
References
- Laura, Q.M.; Chow, M.D. Head and Neck Cancer. N. Engl. J. Med. 2020, 382, 60–72. [Google Scholar] [CrossRef]
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [Green Version]
- WHO. Globocan 2018 Database. Issued by World Health Organization (WHO). Available online: http://gco.iarc.fr/today (accessed on 30 January 2021).
- Mork, J.; Lie, A.K.; Glattre, E.; Clark, S.; Hallmans, G.; Jellum, E.; Koskela, P.; Møller, B.; Pukkala, E.; Schiller, J.T.; et al. Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck. J. Natl. Cancer Inst. 2001, 344, 1125–1131. [Google Scholar] [CrossRef]
- Hashibe, M.; Brennan, P.; Benhamou, S.; Castellsagué, X.; Chen, C.; Curado, M.P.; Dal Maso, L.; Daudt, A.W.; Fabianova, E.; Franceschi, V.W.-F.S.; et al. Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium. J. N. Inst. 2007, 99, 777–789. [Google Scholar] [CrossRef]
- Leemans, C.R.; Braakhuis, B.J.M.; Brakenhoff, R.H. The molecular biology of head and neck cancer. Nat. Rev. Cancer 2010, 11, 9–22. [Google Scholar] [CrossRef]
- Ang, K.K.; Harris, J.; Wheeler, R.; Weber, R.; Rosenthal, D.I.; Nguyen-Tân, P.F.; Westra, W.H.; Chung, C.H.; Jordan, R.C.; Lu, C.; et al. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N. Engl. J. Med. 2010, 363, 24–35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leemans, C.R.; Snijders, P.J.F.; Brakenhoff, R.H. The molecular landscape of head and neck cancer. Nat. Rev. Cancer 2018, 18, 269–282. [Google Scholar] [CrossRef] [PubMed]
- Machiels, J.-P.; Leemans, C.R.; Golusinski, W.; Grau, C.; Licitra, L.; Gregoire, V. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2020, 31, 1462–1475. [Google Scholar] [CrossRef] [PubMed]
- Pai, S.I.; Westra, W.H. Molecular Pathology of Head and Neck Cancer: Implications for Diagnosis, Prognosis, and Treatment. Annu. Rev. Pathol. Mech. Dis. 2009, 4, 49–70. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fakhry, C.; Lacchetti, C.; Rooper, L.M.; Jordan, R.C.; Rischin, D.; Sturgis, E.M.; Bell, D.; Lingen, M.W.; Harichand-Herdt, S.; Thibo, J.; et al. Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J. Clin. Oncol. 2018, 36, 3152–3161. [Google Scholar] [CrossRef]
- Hashim, D.; Boffetta, P. Head and Neck Cancers. Occup. Cancers 2020, 57–105. [Google Scholar] [CrossRef]
- Le, X.; Ferrarotto, R.; Wise-Draper, T.; Gillison, M. Evolving Role of Immunotherapy in Recurrent Metastatic Head and Neck Cancer. J. Natl. Compr. Cancer Netw. 2020, 18, 899–906. [Google Scholar] [CrossRef] [PubMed]
- Sacco, A.G.; Cohen, E.E. Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. J. Clin. Oncol. 2015, 33, 3305–3313. [Google Scholar] [CrossRef] [PubMed]
- Subbiah, V.; Solit, D.; Chan, T.; Kurzrock, R. The FDA approval of pembrolizumab for adult and pediatric patients with tumor mutational burden (TMB) ≥10: A decision centered on empowering patients and their physicians. Ann. Oncol. 2020, 31, 1115–1118. [Google Scholar] [CrossRef] [PubMed]
- Gavrielatou, N.; Doumas, S.; Economopoulou, P.; Foukas, P.G.; Psyrri, A. Biomarkers for immunotherapy response in head and neck cancer. Cancer Treat. Rev. 2020, 84, 101977. [Google Scholar] [CrossRef] [PubMed]
- Economopoulou, P.; De Bree, R.; Kotsantis, I.; Psyrri, A. Diagnostic Tumor Markers in Head and Neck Squamous Cell Carcinoma (HNSCC) in the Clinical Setting. Front. Oncol. 2019, 9, 827. [Google Scholar] [CrossRef] [PubMed]
- Mehanna, H.; Rischin, D.; Wong, S.J.; Gregoire, V.; Ferris, R.; Waldron, J.; Le, Q.-T.; Forster, M.; Gillison, M.; Laskar, S.; et al. De-Escalation After De-Escalate and RTOG 1016: A Head and Neck Cancer InterGroup Framework for Future De-Escalation Studies. J. Clin. Oncol. 2020, 38, 2552–2557. [Google Scholar] [CrossRef]
- Poeta, M.L.; Manola, J.; Goldwasser, M.A.; Forastiere, A.; Benoit, N.; Califano, J.A.; Ridge, J.A.; Goodwin, J.; Kenady, D.; Saunders, J.; et al. TP53Mutations and Survival in Squamous-Cell Carcinoma of the Head and Neck. N. Engl. J. Med. 2007, 357, 2552–2561. [Google Scholar] [CrossRef] [Green Version]
- Kern, S.E. Why Your New Cancer Biomarker May Never Work: Recurrent Patterns and Remarkable Diversity in Biomarker Failures. Cancer Res. 2012, 72, 6097–6101. [Google Scholar] [CrossRef] [Green Version]
- Hunt, J.L. Applications of molecular testing in surgical pathology of the head and neck. Mod. Pathol. 2017, 30, S104–S111. [Google Scholar] [CrossRef] [Green Version]
- Mandal, R.; Şenbabaoğlu, Y.; Desrichard, A.; Havel, J.J.; Dalin, M.G.; Riaz, N.; Lee, K.-W.; Ganly, I.; Hakimi, A.A.; Chan, T.A.; et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 2016, 1, e89829. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferris, R.L. Immunology and Immunotherapy of Head and Neck Cancer. J. Clin. Oncol. 2015, 33, 3293–3304. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [Green Version]
- Bruni, D.; Angell, H.K.; Galon, J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat. Rev. Cancer 2020, 20, 662–680. [Google Scholar] [CrossRef] [PubMed]
- Reichert, T.E.; Rabinowich, H.; Johnson, J.T.; Whiteside, T.L. Mechanisms Responsible for Signaling and Functional Defects. J. Immunother. 1998, 21, 295–306. [Google Scholar] [CrossRef]
- Reichert, T.E.; Strauss, L.; Wagner, E.M.; Gooding, W.; Whiteside, T.L. Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin. Cancer Res. 2002, 8, 3137–3145. [Google Scholar] [PubMed]
- Upreti, D.; Zhang, M.-L.; Bykova, E.; Kung, S.K.P.; Pathak, K.A. Change in CD3ζ-chain expression is an independent predictor of disease status in head and neck cancer patients. Int. J. Cancer 2016, 139, 122–129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sakakura, K.; Chikamatsu, K.; Takahashi, K.; Whiteside, T.L.; Furuya, N. Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck. Cancer Immunol. Immunother. 2005, 55, 151–159. [Google Scholar] [CrossRef]
- Hoffmann, T.K.; Dworacki, G.; Tsukihiro, T.; Meidenbauer, N.; Gooding, W.; Johnson, J.T.; Whiteside, T.L. Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin. Cancer Res. 2002, 8, 2553. [Google Scholar] [PubMed]
- De Ruiter, E.J.; Ooft, M.L.; Devriese, L.A.; Willems, S.M. The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis. OncoImmunology 2017, 6, e1356148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strauss, L.; Bergmann, C.; Szczepanski, M.J.; Gooding, W.E.; Johnson, J.T.; Whiteside, T.L. A Unique Subset of CD4+CD25highFoxp3+ T Cells Secreting Interleukin-10 and Transforming Growth Factor-β1 Mediates Suppression in the Tumor Microenvironment. Clin. Cancer Res. 2007, 13, 4345–4354. [Google Scholar] [CrossRef] [Green Version]
- Bergmann, C.; Strauss, L.; Wang, Y.; Szczepanski, M.J.; Lang, S.; Johnson, J.T.; Whiteside, T.L. T Regulatory Type 1 Cells in Squamous Cell Carcinoma of the Head and Neck: Mechanisms of Suppression and Expansion in Advanced Disease. Clin. Cancer Res. 2008, 14, 3706–3715. [Google Scholar] [CrossRef] [Green Version]
- Oweida, A.; Hararah, M.K.; Phan, A.V.; Binder, D.C.; Bhatia, S.; Lennon, S.; Bukkapatnam, S.; Van Court, B.; Uyanga, N.; Darragh, L.; et al. Resistance to Radiotherapy and PD-L1 Blockade Is Mediated by TIM-3 Upregulation and Regulatory T-Cell Infiltration. Clin. Cancer Res. 2018, 24, 5368–5380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jie, H.-B.; Gildenerleapman, N.; Li, J.; Srivastava, R.M.; Gibson, S.P.; Whiteside, T.L.; Ferris, R.L. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br. J. Cancer 2013, 109, 2629–2635. [Google Scholar] [CrossRef] [PubMed]
- Seminerio, I.; Descamps, G.; Dupont, S.; De Marrez, L.; Laigle, J.-A.; Lechien, J.R.; Kindt, N.; Journe, F.; Saussez, S. Infiltration of FoxP3+ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Cancers 2019, 11, 227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Badoual, C.; Hans, S.; Rodriguez, J.; Peyrard, S.; Klein, C.; Agueznay, N.E.H.; Mosseri, V.; Laccourreye, O.; Bruneval, P.; Fridman, W.H.; et al. Prognostic Value of Tumor-Infiltrating CD4+ T-Cell Subpopulations in Head and Neck Cancers. Clin. Cancer Res. 2006, 12, 465–472. [Google Scholar] [CrossRef] [Green Version]
- Shang, B.; Liu, Y.; Jiang, S.-J.; Liu, Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: A systematic review and meta-analysis. Sci. Rep. 2015, 5, 15179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lang, S.; Bruderek, K.; Kaspar, C.; Höing, B.; Kanaan, O.; Dominas, N.; Hussain, T.; Droege, F.; Eyth, C.; Hadaschik, B.; et al. Clinical Relevance and Suppressive Capacity of Human Myeloid-Derived Suppressor Cell Subsets. Clin. Cancer Res. 2018, 24, 4834–4844. [Google Scholar] [CrossRef] [Green Version]
- Greene, S.; Robbins, Y.; Mydlarz, W.K.; Huynh, A.P.; Schmitt, N.C.; Friedman, J.; Horn, L.A.; Palena, C.; Schlom, J.; Maeda, D.Y.; et al. Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models. Clin. Cancer Res. 2020, 26, 1420–1431. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mantovani, A.; Sica, A.; Sozzani, S.; Allavena, P.; Vecchi, A.; Locati, M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004, 25, 677–686. [Google Scholar] [CrossRef]
- She, L.; Qin, Y.; Wang, J.; Liu, C.; Zhu, G.; Li, G.; Wei, M.; Chen, C.; Liu, G.; Zhang, D.; et al. Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck. Cancer Cell Int. 2018, 18, 120. [Google Scholar] [CrossRef] [PubMed]
- Troiano, G.; Caponio, V.C.A.; Adipietro, I.; Tepedino, M.; Santoro, R.; Laino, L.; Russo, L.L.; Cirillo, N.; Muzio, L.L. Prognostic significance of CD68+ and CD163+ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol. 2019, 93, 66–75. [Google Scholar] [CrossRef] [PubMed]
- Kumar, A.T.; Knops, A.; Swendseid, B.; Martinez-Outschoom, U.; Harshyne, L.; Philp, N.; Rodeck, U.; Luginbuhl, A.; Cognetti, D.; Johnson, J.; et al. Prognostic Significance of Tumor-Associated Macrophage Content in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis. Front. Oncol. 2019, 9, 656. [Google Scholar] [CrossRef] [PubMed]
- Bu, L.-L.; Yu, G.-T.; Deng, W.-W.; Mao, L.; Liu, J.-F.; Ma, S.-R.; Fan, T.-F.; Hall, B.; Kulkarni, A.B.; Zhang, W.-F.; et al. Targeting STAT3 signaling reduces immunosuppressive myeloid cells in head and neck squamous cell carcinoma. OncoImmunology 2016, 5, e1130206. [Google Scholar] [CrossRef]
- Lathers, D. Increased aberrance of cytokine expression in plasma of patients with more advanced squamous cell carcinoma of the head and neck. Cytokine 2004, 25, 220–228. [Google Scholar] [CrossRef]
- Allen, C.T.; A Duffy, S.; Teknos, T.N.; Islam, M.; Chen, Z.; Albert, P.S.; Wolf, G.T.; Van Waes, C. Nuclear Factor-κB–Related Serum Factors as Longitudinal Biomarkers of Response and Survival in Advanced Oropharyngeal Carcinoma. Clin. Cancer Res. 2007, 13, 3182–3190. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Medeiros, M.C.; Banerjee, R.; Liu, M.; Anovazzi, G.; D’Silva, N.J.; Junior, C.R. HNSCC subverts PBMCs to secrete soluble products that promote tumor cell proliferation. Oncotarget 2017, 8, 60860–60874. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- White, R.A.; Malkoski, S.P.; Wang, X.-J. TGFβ signaling in head and neck squamous cell carcinoma. Oncogene 2010, 29, 5437–5446. [Google Scholar] [CrossRef] [Green Version]
- Bornstein, S.; Schmidt, M.; Choonoo, G.; Levin, T.; Gray, J.; Thomas, C.R., Jr.; Wong, M.; McWeeney, S. IL-10 and integrin signaling pathways are associated with head and neck cancer progression. BMC Genom. 2016, 17, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duffy, S.A.; Taylor, J.M.G.; Terrell, J.E.; Islam, M.; Li, Y.; Fowler, K.E.; Wolf, G.T.; Teknos, T.N. Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer 2008, 113, 750–757. [Google Scholar] [CrossRef] [PubMed]
- Tsai, M.-S.; Chen, W.-C.; Lu, C.-H.; Chen, M.-F. The prognosis of head and neck squamous cell carcinoma related to immunosuppressive tumor microenvironment regulated by IL-6 signaling. Oral Oncol. 2019, 91, 47–55. [Google Scholar] [CrossRef] [PubMed]
- Bergmann, C.; Strauss, L.; Zeidler, R.; Lang, S.; Whiteside, T.L. Expansion of Human T Regulatory Type 1 Cells in the Microenvironment of Cyclooxygenase 2 Overexpressing Head and Neck Squamous Cell Carcinoma. Cancer Res. 2007, 67, 8865–8873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Camacho, M.; León, X.; Fernández-Figueras, M.-T.; Quer, M.; Vila, L. Prostaglandin E2pathway in head and neck squamous cell carcinoma. Head Neck 2008, 30, 1175–1181. [Google Scholar] [CrossRef]
- Lang, S.; Tiwari, S.; Andratschke, M.; Loehr, I.; Lauffer, L.; Bergmann, C.; Mack, B.; Lebeau, A.; Moosmann, A.; Whiteside, T.L.; et al. Immune restoration in head and neck cancer patients after in vivo COX-2 inhibition. Cancer Immunol. Immunother. 2007, 56, 1645–1652. [Google Scholar] [CrossRef]
- Gallo, O.; Franchi, A.; Magnelli, L.; Sardi, I.; Vannacci, A.; Boddit, V.; Chiarugi, V.; Masini, E. Cyclooxygenase-2 Pathway Correlates with VEGF Expression in Head and Neck Cancer. Implications for Tumor Angiogenesis and Metastasis. Neoplasia 2001, 3, 53–61. [Google Scholar] [CrossRef] [Green Version]
- Kyzas, P.A.; Cunha, I.W.; Ioannidis, J.P. Prognostic Significance of Vascular Endothelial Growth Factor Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis. Clin. Cancer Res. 2005, 11, 1434–1440. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le, Q.-T.; Shi, G.; Cao, H.; Nelson, D.W.; Wang, Y.; Chen, E.Y.; Zhao, S.; Kong, C.; Richardson, D.; O’Byrne, K.J.; et al. Galectin-1: A Link Between Tumor Hypoxia and Tumor Immune Privilege. J. Clin. Oncol. 2005, 23, 8932–8941. [Google Scholar] [CrossRef] [Green Version]
- Maybruck, B.T.; Pfannenstiel, L.W.; Diaz-Montero, M.; Gastman, B.R. Tumor-derived exosomes induce CD8+ T cell suppressors. J. Immunother. Cancer 2017, 5, 65. [Google Scholar] [CrossRef]
- Nambiar, D.K.; Aguilera, T.; Cao, H.; Kwok, S.; Kong, C.; Bloomstein, J.; Wang, Z.; Rangan, V.S.; Jiang, D.; Von Eyben, R.; et al. Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance. J. Clin. Investig. 2019, 129, 5553–5567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Network, T.C.G.A. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nat. Cell Biol. 2015, 517, 576–582. [Google Scholar] [CrossRef] [Green Version]
- Ogino, T.; Shigyo, H.; Ishii, H.; Katayama, A.; Miyokawa, N.; Harabuchi, Y.; Ferrone, S. HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker. Cancer Res. 2006, 66, 9281–9289. [Google Scholar] [CrossRef] [Green Version]
- López-Albaitero, A.; Nayak, J.V.; Ogino, T.; Machandia, A.; Gooding, W.; DeLeo, A.B.; Ferrone, S.; Ferris, R.L. Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL. J. Immunol. 2006, 176, 3402–3409. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, L.; Mudianto, T.; Ma, X.; Riley, R.; Uppaluri, R. Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti–PD-1 Resistance in Head and Neck Cancer. Clin. Cancer Res. 2019, 26, 290–300. [Google Scholar] [CrossRef] [Green Version]
- Rotte, A.; Jin, J.; Lemaire, V. Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy. Ann. Oncol. 2018, 29, 71–83. [Google Scholar] [CrossRef] [Green Version]
- Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of Antitumor Immunity by CTLA-4 Blockade. Science 1996, 271, 1734–1736. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, G.-T.; Bu, L.-L.; Zhao, Y.-Y.; Mao, L.; Deng, W.-W.; Wu, T.-F.; Zhang, W.-F.; Sun, Z.-J. CTLA4 blockade reduces immature myeloid cells in head and neck squamous cell carcinoma. OncoImmunology 2016, 5, e1151594. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Z.; Wu, V.H.; Allevato, M.M.; Gilardi, M.; He, Y.; Callejas-Valera, J.L.; Vitale-Cross, L.; Martin, D.; Amornphimoltham, P.; McDermott, J.; et al. Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4. Nat. Commun. 2019, 10, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Jie, H.-B.; Schuler, P.J.; Lee, S.C.; Srivastava, R.M.; Argiris, A.; Ferrone, S.; Whiteside, T.L.; Ferris, R.L. CTLA-4+ Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis. Cancer Res. 2015, 75, 2200–2210. [Google Scholar] [CrossRef] [Green Version]
- Gao, Y.; Nihira, N.T.; Bu, X.; Chu, C.; Zhang, J.; Kolodziejczyk, A.; Fan, Y.; Chan, N.T.; Ma, L.; Liu, J.; et al. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat. Cell Biol. 2020, 22, 1–12. [Google Scholar] [CrossRef]
- Dammeijer, F.; Van Gulijk, M.; Mulder, E.E.; Lukkes, M.; Klaase, L.; Bosch, T.V.D.; Van Nimwegen, M.; Lau, S.P.; Latupeirissa, K.; Schetters, S.; et al. The PD-1/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes. Cancer Cell 2020, 38, 685–700.e8. [Google Scholar] [CrossRef]
- Karpathiou, G.; Casteillo, F.; Giroult, J.-B.; Forest, F.; Fournel, P.; Monaya, A.; Froudarakis, M.; Dumollard, J.M.; Prades, J.M.; Peoc’H, M. Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: Immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics. Oncotarget 2016, 8, 19310–19322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ock, C.-Y.; Kim, S.; Keam, B.; Kim, M.; Kim, T.M.; Kim, J.-H.; Jeon, Y.K.; Lee, J.-S.; Kwon, S.K.; Hah, J.H.; et al. PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget 2016, 7, 15901–15914. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Concha-Benavente, F.; Srivastava, R.M.; Trivedi, S.; Lei, Y.; Chandran, U.R.; Seethala, R.R.; Freeman, G.J.; Ferris, R.L. Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNγ That Induce PD-L1 Expression in Head and Neck Cancer. Cancer Res. 2016, 76, 1031–1043. [Google Scholar] [CrossRef] [Green Version]
- Badoual, C.; Hans, S.; Merillon, N.; Van Ryswick, C.; Ravel, P.; Benhamouda, N.; Levionnois, E.; Nizard, M.; Si-Mohamed, A.; Besnier, N.; et al. PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer. Cancer Res. 2012, 73, 128–138. [Google Scholar] [CrossRef] [Green Version]
- Theodoraki, M.-N.; Yerneni, S.S.; Hoffmann, T.K.; Gooding, W.E.; Whiteside, T.L. Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients. Clin. Cancer Res. 2018, 24, 896–905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Punt, S.; Thijssen, V.L.; Vrolijk, J.; De Kroon, C.D.; Gorter, A.; Jordanova, E.S. Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer. PLoS ONE 2015, 10, e0129119. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Workman, C.J.; Dugger, K.J.; Vignali, D.A.A. Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3. J. Immunol. 2002, 169, 5392–5395. [Google Scholar] [CrossRef] [Green Version]
- Liang, B.; Workman, C.; Lee, J.; Chew, C.; Dale, B.M.; Colonna, L.; Flores, M.; Li, N.; Schweighoffer, E.; Greenberg, S.; et al. Regulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II. J. Immunol. 2008, 180, 5916–5926. [Google Scholar] [CrossRef] [Green Version]
- Kouo, T.S.; Huang, L.; Pucsek, A.B.; Cao, M.; Solt, S.; Armstrong, T.D.; Jaffee, E.M. Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells. Cancer Immunol. Res. 2015, 3, 412–423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deng, W.-W.; Mao, L.; Yu, G.-T.; Bu, L.-L.; Ma, S.-R.; Liu, B.; Gutkind, J.S.; Kulkarni, A.B.; Zhang, W.-F.; Sun, Z.-J. LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma. OncoImmunology 2016, 5, e1239005. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Somasundaram, A.; Cillo, A.R.; Lampenfeld, C.; Oliveri, L.; Velez, M.A.; Joyce, S.; Calderon, M.J.; Dadey, R.; Rajasundaram, D.; Normolle, D.P.; et al. Systemic Immune Dysfunction in Cancer Patients Driven by IL6 and IL8 Induction of an Inhibitory Receptor Module in Peripheral CD8+ T Cells. bioRxiv 2020. [Google Scholar] [CrossRef]
- Liu, J.-F.; Wu, L.; Yang, L.-L.; Deng, W.-W.; Mao, L.; Wu, H.; Zhang, W.-F.; Sun, Z.-J. Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer. J. Exp. Clin. Cancer Res. 2018, 37, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Liu, J.-F.; Ma, S.-R.; Mao, L.; Bu, L.-L.; Yu, G.-T.; Li, Y.-C.; Huang, C.-F.; Deng, W.-W.; Kulkarni, A.B.; Zhang, W.-F.; et al. T-cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer. Mol. Oncol. 2017, 11, 235–247. [Google Scholar] [CrossRef] [Green Version]
- Wu, L.; Mao, L.; Liu, J.-F.; Chen, L.; Yu, G.-T.; Yang, L.-L.; Wu, H.; Bu, L.-L.; Kulkarni, A.B.; Zhang, W.-F.; et al. Blockade of TIGIT/CD155 Signaling Reverses T-cell Exhaustion and Enhances Antitumor Capability in Head and Neck Squamous Cell Carcinoma. Cancer Immunol. Res. 2019, 7, 1700–1713. [Google Scholar] [CrossRef]
- Gameiro, S.F.; Ghasemi, F.; Barrett, J.W.; Koropatnick, J.; Nichols, A.C.; Mymryk, J.S.; Vareki, S.M. Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy. OncoImmunology 2018, 7, e1498439. [Google Scholar] [CrossRef] [Green Version]
- Seiwert, T.Y.; Burtness, B.; Mehra, R.; Weiss, J.; Berger, R.; Eder, J.P.; Heath, K.; McClanahan, T.; Lunceford, J.; Gause, C.; et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): An open-label, multicentre, phase 1b trial. Lancet Oncol. 2016, 17, 956–965. [Google Scholar] [CrossRef]
- Chow, L.Q.; Haddad, R.; Gupta, S.; Mahipal, A.; Mehra, R.; Tahara, M.; Berger, R.; Eder, J.P.; Burtness, B.; Lee, S.-H.; et al. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J. Clin. Oncol. 2016, 34, 3838–3845. [Google Scholar] [CrossRef]
- Bauml, J.; Seiwert, T.Y.; Pfister, D.G.; Worden, F.; Liu, S.V.; Gilbert, J.; Saba, N.F.; Weiss, J.; Wirth, L.; Sukari, A.; et al. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J. Clin. Oncol. 2017, 35, 1542–1549. [Google Scholar] [CrossRef] [PubMed]
- Ferris, R.L.; Blumenschein, G., Jr.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.; Kasper, S.; Vokes, E.E.; Even, C.; et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N. Engl. J. Med. 2016, 375, 1856–1867. [Google Scholar] [CrossRef] [PubMed]
- Cohen, E.E.W.; Soulières, D.; Le Tourneau, C.; Dinis, J.; Licitra, L.; Ahn, M.-J.; Soria, A.; Machiels, J.-P.; Mach, N.; Mehra, R.; et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomised, open-label, phase 3 study. Lancet 2019, 393, 156–167. [Google Scholar] [CrossRef]
- Burtness, B.; Harrington, K.J.; Greil, R.; Soulières, D.; Tahara, M.; de Castro, G.; Psyrri, A.; Basté, N.; Neupane, P.; Bratland, Å.; et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet 2019, 394, 1915–1928. [Google Scholar] [CrossRef]
- Yu, Y.; Lee, N.Y. JAVELIN Head and Neck 100: A Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Futur. Oncol. 2019, 15, 687–694. [Google Scholar] [CrossRef]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Callahan, M.K.; Wolchok, J.D.; Allison, J.P. Anti–CTLA-4 Antibody Therapy: Immune Monitoring During Clinical Development of a Novel Immunotherapy. Semin. Oncol. 2010, 37, 473–484. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferris, R.; Haddad, R.; Even, C.; Tahara, M.; Dvorkin, M.; Ciuleanu, T.; Clement, P.; Mesia, R.; Kutukova, S.; Zholudeva, L.; et al. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann. Oncol. 2020, 31, 942–950. [Google Scholar] [CrossRef]
- Klinghammer, K.F.; Gauler, T.C.; Stromberger, C.; Kofla, G.; De Wit, M.; Gollrad, J.; Rauer, I.; Martus, P.; Tinhofer, I.; Budach, V.; et al. DURTRERAD: A phase II open-label study evaluating feasibility and efficacy of durvalumab (D) and durvalumab and tremelimumab (DT) in combination with radiotherapy (RT) in non-resectable locally advanced HPV-negative HNSCC—Results of the preplanned feasibility interim analysis. J. Clin. Oncol. 2020, 38, 6574. [Google Scholar] [CrossRef]
- Machiels, J.-P.; Tao, Y.; Burtness, B.; Tahara, M.; Licitra, L.; Rischin, D.; Waldron, J.; Simon, C.; Gregoire, V.; Harrington, K.; et al. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Futur. Oncol. 2020, 16, 1235–1243. [Google Scholar] [CrossRef]
- Massarelli, E.; William, W.; Johnson, F.; Kies, M.; Ferrarotto, R.; Guo, M.; Feng, L.; Lee, J.J.; Tran, H.; Kim, Y.U.; et al. Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16–Related Cancer. JAMA Oncol. 2019, 5, 67–73. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le Tourneau, C.; Delord, J.-P.; Cassier, P.; Loirat, D.; Tavernaro, A.; Bastien, B.; Bendjama, K. Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers. Ann. Oncol. 2019, 30, v494–v495. [Google Scholar] [CrossRef]
- Stafford, M.; Kaczmar, J. The neoadjuvant paradigm reinvigorated: A review of pre-surgical immunotherapy in HNSCC. Cancers Head Neck 2020, 5, 4–9. [Google Scholar] [CrossRef]
- Uppaluri, R.; Campbell, K.M.; Egloff, A.M.; Zolkind, P.; Skidmore, Z.L.; Nussenbaum, B.; Paniello, R.C.; Rich, J.T.; Jackson, R.; Pipkorn, P.; et al. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase 2 Trial. Clin. Cancer Res. 2020, 26, 5140–5152. [Google Scholar] [CrossRef] [PubMed]
- Ferris, R.; Gonçalves, A.; Baxi, S.; Martens, U.; Gauthier, H.; Langenberg, M.; Spanos, W.; Leidner, R.; Kang, H.; Russell, J.; et al. An open-label, multicohort, phase 1/2 study in patients with virus-associated cancers (CheckMate 358): Safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck (SCCHN). Ann. Oncol. 2017, 28, v628–v629. [Google Scholar] [CrossRef] [Green Version]
- Wise-Draper, T.M.; Old, M.O.; Worden, F.P.; O’Brien, P.E.; Cohen, E.E.; Dunlap, N.; Mierzwa, M.L.; Casper, K.; Palackdharry, S.; Hinrichs, B.; et al. Phase II multi-site investigation of neoadjuvant pembrolizumab and adjuvant concurrent radiation and pembrolizumab with or without cisplatin in resected head and neck squamous cell carcinoma. J. Clin. Oncol. 2018, 36, 6017. [Google Scholar] [CrossRef]
- Wong, D.J.; Fayette, J.; Guo, Y.; Kowgier, M.; Cohen, E.; Nin, R.M.; Dechaphunkul, A.; Prabhash, K.; Geiger, J.; Bishnoi, S.; et al. Abstract CT123: IMvoke010: Randomized Phase III study of atezolizumab as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN). In Clinical Trials; American Association for Cancer Research (AACR): Philadelphia, PA, USA, 2019. [Google Scholar]
- Busch, C.-J.; Muenscher, A.; Betz, C.S.; Dogan, V.; Schafhausen, P.; Bokemeyer, C.; Binder, M. Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy. J. Clin. Oncol. 2019, 37, TPS6095. [Google Scholar] [CrossRef]
- Cohen, E.E.W.; Bell, R.B.; Bifulco, C.B.; Burtness, B.; Gillison, M.L.; Harrington, K.J.; Le, Q.-T.; Lee, N.Y.; Leidner, R.; Lewis, R.L.; et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J. Immunother. Cancer 2019, 7, 184. [Google Scholar] [CrossRef] [Green Version]
- Hegde, P.S.; Chen, D.S. Top 10 Challenges in Cancer Immunotherapy. Immunity 2020, 52, 17–35. [Google Scholar] [CrossRef] [PubMed]
- Mckean, W.B.; Moser, J.C.; Rimm, D.; Hu-Lieskovan, S. Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges. Am. Soc. Clin. Oncol. Educ. Book 2020, 40, e275–e291. [Google Scholar] [CrossRef] [PubMed]
- Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Bartlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017, 357, 409–413. [Google Scholar] [CrossRef] [Green Version]
- Havel, J.J.; Chowell, D.; Chan, T.A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat. Rev. Cancer 2019, 19, 133–150. [Google Scholar] [CrossRef]
- Samstein, R.M.; Lee, C.-H.; Shoushtari, A.N.; Hellmann, M.D.; Shen, R.; Janjigian, Y.Y.; Barron, D.A.; Zehir, A.; Jordan, E.J.; Omuro, A.; et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 2019, 51, 202–206. [Google Scholar] [CrossRef] [PubMed]
- Cristescu, R.; Mogg, R.; Ayers, M.; Albright, A.; Murphy, E.; Yearley, J.; Sher, X.; Liu, X.Q.; Lu, H.; Nebozhyn, M.; et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science 2018, 362, eaar3593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De La Iglesia, J.V.; Slebos, R.J.; Martin-Gomez, L.; Wang, X.; Teer, J.K.; Tan, A.C.; Gerke, T.A.; Aden-Buie, G.; Van Veen, T.; Masannat, J.; et al. Effects of Tobacco Smoking on the Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma. Clin. Cancer Res. 2020, 26, 1474–1485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Desrichard, A.; Kuo, F.; Chowell, D.; Lee, K.-W.; Riaz, N.; Wong, R.J.; A Chan, T.; Morris, L.G.T. Tobacco Smoking-Associated Alterations in the Immune Microenvironment of Squamous Cell Carcinomas. J. Natl. Cancer Inst. 2018, 110, 1386–1392. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015, 348, 124–128. [Google Scholar] [CrossRef] [Green Version]
- Kreimer, A.R.; Clifford, G.M.; Boyle, P.; Franceschi, S. Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review. Cancer Epidemiol. Biomark. Prev. 2005, 14, 467–475. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Davis, A.A.; Patel, V.G. The role of PD-L1 expression as a predictive biomarker: An analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J. Immunother. Cancer 2019, 7, 1–8. [Google Scholar] [CrossRef]
- Rasmussen, J.H.; Lelkaitis, G.; Håkansson, K.; Vogelius, I.R.; Johannesen, H.H.; Fischer, B.M.; Bentzen, S.M.; Specht, L.; Kristensen, C.A.; Von Buchwald, C.; et al. Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br. J. Cancer 2019, 120, 1003–1006. [Google Scholar] [CrossRef] [Green Version]
- Hong, L.; Negrao, M.V.; Dibaj, S.S.; Chen, R.; Reuben, A.; Bohac, J.M.; Liu, X.; Skoulidis, F.; Gay, C.M.; Cascone, T.; et al. Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC. J. Thorac. Oncol. 2020, 15, 1449–1459. [Google Scholar] [CrossRef]
- De Ruiter, E.J.; Mulder, F.J.; Koomen, B.M.; Speel, E.-J.; Hout, M.F.C.M.V.D.; De Roest, R.H.; Bloemena, E.; Devriese, L.A.; Willems, S.M. Comparison of three PD-L1 immunohistochemical assays in head and neck squamous cell carcinoma (HNSCC). Mod. Pathol. 2020, 1–8. [Google Scholar] [CrossRef]
- Daassi, D.; Mahoney, K.M.; Freeman, G.J. The importance of exosomal PDL1 in tumour immune evasion. Nat. Rev. Immunol. 2020, 20, 209–215. [Google Scholar] [CrossRef]
- Theodoraki, M.-N.; Yerneni, S.; Gooding, W.E.; Ohr, J.; Clump, D.A.; Bauman, J.E.; Ferris, R.L.; Whiteside, T.L. Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT. OncoImmunology 2019, 8, e1593805. [Google Scholar] [CrossRef]
- Ayers, M.; Lunceford, J.; Nebozhyn, M.; Murphy, E.; Loboda, A.; Kaufman, D.R.; Albright, A.; Cheng, J.D.; Kang, S.P.; Shankaran, V.; et al. IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Investig. 2017, 127, 2930–2940. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.-P.; Wang, Y.-Q.; Lv, J.-W.; Li, Y.-Q.; Chua, M.; Le, Q.-T.; Lee, N.; Colevas, A.D.; Seiwert, T.; Hayes, D.; et al. Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: Implications for immunotherapy. Ann. Oncol. 2019, 30, 68–75. [Google Scholar] [CrossRef]
- Ren, X.; Kang, B.; Zhang, Z. Understanding tumor ecosystems by single-cell sequencing: Promises and limitations. Genome Biol. 2018, 19, 211. [Google Scholar] [CrossRef]
- Puram, S.V.; Tirosh, I.; Parikh, A.S.; Patel, A.P.; Yizhak, K.; Gillespie, S.; Rodman, C.; Luo, C.L.; Mroz, E.A.; Emerick, K.S.; et al. Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer. Cell 2017, 171, 1611–1624.e24. [Google Scholar] [CrossRef] [Green Version]
- Börnigen, D.; Ren, B.; Pickard, R.; Li, J.; Ozer, E.; Hartmann, E.M.; Xiao, W.; Tickle, T.; Rider, J.; Gevers, D.; et al. Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer. Sci. Rep. 2017, 7, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Hayes, R.B.; Ahn, J.; Fan, X.; Peters, B.A.; Ma, Y.; Yang, L.; Agalliu, I.; Burk, R.D.; Ganly, I.; Purdue, M.P.; et al. Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer. JAMA Oncol. 2018, 4, 358–365. [Google Scholar] [CrossRef] [PubMed]
- Garrett, W.S. Cancer and the microbiota. Science 2015, 348, 80–86. [Google Scholar] [CrossRef] [Green Version]
- Routy, B.; Gopalakrishnan, V.; Daillère, R.; Zitvogel, L.; Wargo, J.A.; Kroemer, G. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 2018, 15, 382–396. [Google Scholar] [CrossRef] [PubMed]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef] [Green Version]
- Zheng, Y.; Wang, T.; Tu, X.; Huang, Y.; Zhang, H.; Tan, D.; Jiang, W.; Cai, S.; Zhao, P.; Song, R.; et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J. Immunother. Cancer 2019, 7, 193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; He, Z.; Wang, X.; Li, H.; Liu, X.-S. Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction. eLife 2019, 8, 8. [Google Scholar] [CrossRef]
- Charoentong, P.; Finotello, F.; Angelova, M.; Mayer, C.; Efremova, M.; Rieder, D.; Hackl, H.; Trajanoski, Z. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep. 2017, 18, 248–262. [Google Scholar] [CrossRef] [Green Version]
- Lu, S.; Stein, J.E.; Rimm, D.L.; Wang, D.W.; Bell, J.M.; Johnson, D.B.; Sosman, J.A.; Schalper, K.A.; Anders, R.A.; Wang, H.; et al. Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade. JAMA Oncol. 2019, 5, 1195–1204. [Google Scholar] [CrossRef]
- Van Schalkwyk, M.C.I.; Papa, S.E.; Jeannon, J.-P.; Urbano, T.G.; Spicer, J.F.; Maher, J. Design of a Phase I Clinical Trial to Evaluate Intratumoral Delivery of ErbB-Targeted Chimeric Antigen Receptor T-Cells in Locally Advanced or Recurrent Head and Neck Cancer. Hum. Gene Ther. Clin. Dev. 2013, 24, 134–142. [Google Scholar] [CrossRef] [PubMed]
- June, C.H.; O’Connor, R.S.; Kawalekar, O.U.; Ghassemi, S.; Milone, M.C. CAR T cell immunotherapy for human cancer. Science 2018, 359, 1361–1365. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mei, Z.; Zhang, K.; Lam, A.K.; Huang, J.; Qiu, F.; Qiao, B.; Zhang, Y. MUC1 as a target for CAR-T therapy in head and neck squamous cell carinoma. Cancer Med. 2019, 9, 640–652. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Clinical Trial NCT Number | Clinical Trial Title | Status | Interventions | Immune Checkpoint Tested | Clinical Trial Details | Enrollment (Number of Patients) |
---|---|---|---|---|---|---|
NCT04454489 | Quad Shot Radiotherapy in Combination with Immune Checkpoint Inhibition | Not yet recruiting |
| PD-1 | Phase:
| 15 |
NCT03313804 | Priming Immunotherapy in Advanced Disease with Radiation | Recruiting |
| PD-1/ PD-L1 | Phase:
| 57 |
NCT03228667 | QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment with Immune Checkpoint Inhibitors | Recruiting | Cohort 1: Patients who progressed on or after a single-agent ICI after experiencing an initial CR or PR. N-803 + Pembrolizumab or Nivolumab or Atezolizumab or Avelumab or DurvalumabCohort 2 and Cohort 3 only for selected NSCLC patients. Experimental Cohort 4: Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing SD for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy N-803 + Pembrolizumab or Nivolumab or Atezolizumab or Avelumab or Durvalumab Experimental Cohort 5: Patients who experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4 N-803 + Pembrolizumab or Nivolumab or Atezolizumab or Avelumab or Durvalumab + PD-L1 t-haNK | PD-1/ PD-L1 | Phase:
| 636 |
NCT03522584 | Durvalumab, Tremelimumab and Hypofractionated Radiation Therapy in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma | Recruiting |
| PD-L1 CTLA-4 | Phase:
| 20 |
NCT03544723 | Safety and Efficacy of p53 Gene Therapy Combined with Immune Checkpoint Inhibitors in Solid Tumors. | Recruiting |
| PD-1 | Phase:
| 40 |
NCT04282109 | Nivolumab in Combination with Paclitaxel in Subjects with Head and Neck Cancer Unable for Cisplatin- Study to Assess the Efficacy and Safety of based Chemotherapy (NIVOTAX) | Recruiting |
| PD-1 | Phase:
| 141 |
NCT03944915 | De-Escalation Therapy for Human Papillomavirus Negative Disease | Recruiting |
| PD-1 | Phase:
| 36 |
NCT03426657 | Radiotherapy with Double Checkpoint Blockade of Locally Advanced HNSCC | Recruiting |
| PD-L1 CTLA-4 | Phase:
| 120 |
NCT03841110 | FT500 as Monotherapy and in Combination with Immune Checkpoint Inhibitors in Subjects with Advanced Solid Tumors | Recruiting |
| PD-1/ PD-L1 | Phase:
| 76 |
NCT03377400 | Definitive CCRT Combined with Durvalumab and Tremelimumab for Inoperable Esophageal Cancer | Active, not Recruiting |
| PD-L1 CTLA-4 | Phase:
| 40 |
NCT03673735 | Maintenance Immune Check-point Inhibitor Following Post-Operative Chemo-radiation in Subjects with HPV-negative HNSCC | Not yet recruiting |
| PD-L1 | Phase:
| 650 |
NCT04393506 | Inductive Camrelizumab and Apatinib for Patients with Locally Advanced and Resectable Oral Squamous Cell Carcinoma | Recruiting |
| PD-1 | Phase:
| 20 |
NCT03946358 | Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL) | Recruiting |
| PD-L1 | Phase:
| 47 |
NCT04058145 | AMD3100 Plus Pembrolizumab in Immune Checkpoint Blockade Refractory Head and Neck Squamous Cell Carcinoma | Recruiting |
| PD-1 | Phase:
| 57 |
NCT04080804 | Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination with Relatlimab or Ipilimumab in Head and Neck Cancer | Recruiting |
| PD-1 CTLA-4 LAG-3 | Phase:
| 60 |
NCT03690986 | VX15/2503 in Combination with Ipilimumab or Nivolumab in Patients with Head and Neck Cancer | Recruiting |
| PD-1 CTLA-4 | Phase:
| 36 |
NCT02718820 | Pembrolizumab Plus Docetaxel for the Treatment of Recurrent or Metastatic Head and Neck Cancer | Active, not recruiting |
| PD-1 | Phase:
| 22 |
NCT03684785 | Intratumoral Cavrotolimod Combined with Pembrolizumab or Cemiplimab in Patients with Advanced Solid Tumors | Recruiting |
| PD-1 | Phase:
| 130 |
NCT03212469 | A Trial of Durvalumab and Tremelimumab in Combination with SBRT in Patients with Metastatic Cancer (ABBIMUNE) | Recruiting |
| PD-1 CTLA-4 | Phase:
| 55 |
NCT03818061 | Atezolizumab and Bevacizumab in Patients with Recurrent or Metastatic Squamous-Cell Carcinoma of the Head and Neck (ATHENA) | Recruiting |
| PD-L1 | Phase:
| 110 |
NCT03829501 | Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer | Recruiting |
| PD-L1 ICOS | Phase:
| 412 |
NCT02551159 | Phase III Open Label Study of MEDI 4736 with/without Tremelimumab Versus Standard of Care (SoC) in Recurrent/Metastatic Head and Neck Cancer | Active, not recruiting |
| PD-L1 CTLA-4 | Phase:
| 823 |
NCT03517488 | A Study of XmAb®20717 in Subjects with Selected Advanced Solid Tumors (DUET-2) | Recruiting |
| PD-1 CTLA-4 | Phase:
| 154 |
NCT03693612 | GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors | Recruiting |
| ICOS CTLA-4 | Phase:
| 114 |
NCT02575404 | GR-MD-02 Plus Pembrolizumab in Melanoma, Non-Small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients | Recruiting |
| Gal-3 /LAG3 axis PD-1 | Phase:
| 22 |
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Veigas, F.; Mahmoud, Y.D.; Merlo, J.; Rinflerch, A.; Rabinovich, G.A.; Girotti, M.R. Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma. Cancers 2021, 13, 1018. https://doi.org/10.3390/cancers13051018
Veigas F, Mahmoud YD, Merlo J, Rinflerch A, Rabinovich GA, Girotti MR. Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma. Cancers. 2021; 13(5):1018. https://doi.org/10.3390/cancers13051018
Chicago/Turabian StyleVeigas, Florencia, Yamil D. Mahmoud, Joaquin Merlo, Adriana Rinflerch, Gabriel Adrian Rabinovich, and María Romina Girotti. 2021. "Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma" Cancers 13, no. 5: 1018. https://doi.org/10.3390/cancers13051018