Autophagy in Cancer Immunotherapy
Abstract
:1. Introduction
2. The Induction and Regulation of Autophagy
3. The Role of Autophagy in Cancer Progression
4. Autophagy in Tumor Immune System
4.1. Autophagy in Immune Cells
4.1.1. Autophagy in T cells
4.1.2. Autophagy in B cells
4.1.3. Autophagy in Natural Killer (NK) Cells
4.1.4. Autophagy in Dendritic Cells (DCs)
4.1.5. Autophagy in Macrophages
4.2. Autophagy in Regulating Immune Checkpoint Molecules
4.3. Autophagy in Immune Cytokines
4.3.1. Interleukins
4.3.2. Interferons
4.3.3. Transforming Growth Factor Beta (TGF-β)
4.3.4. Tumor Necrosis Factor Alpha (TNF-α)
5. The Bidirectional Role of Autophagy in Immunotherapy
5.1. Autophagy Enhances the Effects of Immunotherapy
5.2. Autophagy Attenuates the Effects of Immunotherapy
6. The Strategies of Targeting Autophagy to Facilitate Cancer Immunotherapy
7. Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Chen, D.S.; Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 2017, 541, 321–330. [Google Scholar] [CrossRef]
- O’Donnell, J.S.; Teng, M.W.L.; Smyth, M.J. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat. Rev. Clin. Oncol. 2019, 16, 151–167. [Google Scholar] [CrossRef]
- Lei, Y.; Chen, L.; Liu, J.; Zhong, Y.; Deng, L. The MicroRNA-Based Strategies to Combat Cancer Chemoresistance via Regulating Autophagy. Front. Oncol. 2022, 12, 841625. [Google Scholar] [CrossRef]
- Ishimwe, N.; Zhang, W.; Qian, J.; Zhang, Y.; Wen, L. Autophagy regulation as a promising approach for improving cancer immunotherapy. Cancer Lett. 2020, 475, 34–42. [Google Scholar] [CrossRef] [PubMed]
- Galon, J.; Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 2019, 18, 197–218. [Google Scholar] [CrossRef] [PubMed]
- White, E.; Lattime, E.C.; Guo, J.Y. Autophagy Regulates Stress Responses, Metabolism, and Anticancer Immunity. Trends Cancer 2021, 7, 778–789. [Google Scholar] [CrossRef] [PubMed]
- Jiang, G.M.; Tan, Y.; Wang, H.; Peng, L.; Chen, H.T.; Meng, X.J.; Li, L.L.; Liu, Y.; Li, W.F.; Shan, H. The relationship between autophagy and the immune system and its applications for tumor immunotherapy. Mol. Cancer 2019, 18, 17. [Google Scholar] [CrossRef] [PubMed]
- Amaravadi, R.K.; Kimmelman, A.C.; Debnath, J. Targeting Autophagy in Cancer: Recent Advances and Future Directions. Cancer Discov. 2019, 9, 1167–1181. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kundu, M.; Viollet, B.; Guan, K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 2011, 13, 132–141. [Google Scholar] [CrossRef]
- Behrends, C.; Sowa, M.E.; Gygi, S.P.; Harper, J.W. Network organization of the human autophagy system. Nature 2010, 466, 68–76. [Google Scholar] [CrossRef] [Green Version]
- Ge, L.; Melville, D.; Zhang, M.; Schekman, R. The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. Elife 2013, 2, e00947. [Google Scholar] [CrossRef] [PubMed]
- Dooley, H.C.; Razi, M.; Polson, H.E.; Girardin, S.E.; Wilson, M.I.; Tooze, S.A. WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol. Cell 2014, 55, 238–252. [Google Scholar] [CrossRef] [PubMed]
- Walczak, M.; Martens, S. Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation. Autophagy 2013, 9, 424–425. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Hou, Y.; Wang, J.; Chen, X.; Shao, Z.M.; Yin, X.M. Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J. Biol. Chem. 2011, 286, 7327–7338. [Google Scholar] [CrossRef] [PubMed]
- Romanov, J.; Walczak, M.; Ibiricu, I.; Schuchner, S.; Ogris, E.; Kraft, C.; Martens, S. Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation. EMBO J. 2012, 31, 4304–4317. [Google Scholar] [CrossRef] [PubMed]
- Moosavi, M.A.; Djavaheri-Mergny, M. Autophagy: New Insights into Mechanisms of Action and Resistance of Treatment in Acute Promyelocytic leukemia. Int. J. Mol. Sci. 2019, 20, 3559. [Google Scholar] [CrossRef]
- Xia, H.; Green, D.R.; Zou, W. Autophagy in tumour immunity and therapy. Nat. Rev. Cancer 2021, 21, 281–297. [Google Scholar] [CrossRef] [PubMed]
- Shibutani, S.T.; Yoshimori, T. A current perspective of autophagosome biogenesis. Cell Res. 2014, 24, 58–68. [Google Scholar] [CrossRef] [PubMed]
- Kimmelman, A.C.; White, E. Autophagy and Tumor Metabolism. Cell Metab. 2017, 25, 1037–1043. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, S.; Yoshimori, T. New insights into autophagosome-lysosome fusion. J. Cell Sci. 2017, 130, 1209–1216. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mizushima, N.; Levine, B. Autophagy in Human Diseases. N. Engl. J. Med. 2020, 383, 1564–1576. [Google Scholar] [CrossRef] [PubMed]
- Yun, C.W.; Lee, S.H. The Roles of Autophagy in Cancer. Int. J. Mol. Sci. 2018, 19, 3466. [Google Scholar] [CrossRef] [PubMed]
- Herzig, S.; Shaw, R.J. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 2018, 19, 121–135. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.L.; DeLay, M.; Jahangiri, A.; Molinaro, A.M.; Rose, S.D.; Carbonell, W.S.; Aghi, M.K. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res. 2012, 72, 1773–1783. [Google Scholar] [CrossRef] [PubMed]
- Di Conza, G.; Trusso Cafarello, S.; Loroch, S.; Mennerich, D.; Deschoemaeker, S.; Di Matteo, M.; Ehling, M.; Gevaert, K.; Prenen, H.; Zahedi, R.P.; et al. The mTOR and PP2A Pathways Regulate PHD2 Phosphorylation to Fine-Tune HIF1alpha Levels and Colorectal Cancer Cell Survival under Hypoxia. Cell Rep. 2017, 18, 1699–1712. [Google Scholar] [CrossRef] [PubMed]
- Mazure, N.M.; Pouyssegur, J. Atypical BH3-domains of BNIP3 and BNIP3L lead to autophagy in hypoxia. Autophagy 2009, 5, 868–869. [Google Scholar] [CrossRef] [PubMed]
- Rouschop, K.M.; van den Beucken, T.; Dubois, L.; Niessen, H.; Bussink, J.; Savelkouls, K.; Keulers, T.; Mujcic, H.; Landuyt, W.; Voncken, J.W.; et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J. Clin. Investig. 2010, 120, 127–141. [Google Scholar] [CrossRef] [PubMed]
- Poillet-Perez, L.; Despouy, G.; Delage-Mourroux, R.; Boyer-Guittaut, M. Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy. Redox Biol. 2015, 4, 184–192. [Google Scholar] [CrossRef]
- Alexander, A.; Cai, S.L.; Kim, J.; Nanez, A.; Sahin, M.; MacLean, K.H.; Inoki, K.; Guan, K.L.; Shen, J.; Person, M.D.; et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Natl. Acad. Sci. USA 2010, 107, 4153–4158. [Google Scholar] [CrossRef] [PubMed]
- Song, C.; Mitter, S.K.; Qi, X.; Beli, E.; Rao, H.V.; Ding, J.; Ip, C.S.; Gu, H.; Akin, D.; Dunn, W.A., Jr.; et al. Oxidative stress-mediated NFkappaB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy. PLoS ONE 2017, 12, e0171940. [Google Scholar] [CrossRef] [Green Version]
- Morishita, H.; Mizushima, N. Diverse Cellular Roles of Autophagy. Annu. Rev. Cell Dev. Biol. 2019, 35, 453–475. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; He, S.; Ma, B. Autophagy and autophagy-related proteins in cancer. Mol. Cancer 2020, 19, 12. [Google Scholar] [CrossRef] [PubMed]
- Mizushima, N. The ATG conjugation systems in autophagy. Curr. Opin. Cell Biol. 2020, 63, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Qu, X.; Yu, J.; Bhagat, G.; Furuya, N.; Hibshoosh, H.; Troxel, A.; Rosen, J.; Eskelinen, E.L.; Mizushima, N.; Ohsumi, Y.; et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Investig. 2003, 112, 1809–1820. [Google Scholar] [CrossRef]
- Kenific, C.M.; Thorburn, A.; Debnath, J. Autophagy and metastasis: Another double-edged sword. Curr. Opin. Cell Biol. 2010, 22, 241–245. [Google Scholar] [CrossRef]
- Sosa, M.S.; Bragado, P.; Aguirre-Ghiso, J.A. Mechanisms of disseminated cancer cell dormancy: An awakening field. Nat. Rev. Cancer 2014, 14, 611–622. [Google Scholar] [CrossRef] [PubMed]
- Peng, Y.F.; Shi, Y.H.; Shen, Y.H.; Ding, Z.B.; Ke, A.W.; Zhou, J.; Qiu, S.J.; Fan, J. Promoting colonization in metastatic HCC cells by modulation of autophagy. PLoS ONE 2013, 8, e74407. [Google Scholar] [CrossRef]
- Dikic, I.; Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 2018, 19, 349–364. [Google Scholar] [CrossRef]
- Ma, Y.; Galluzzi, L.; Zitvogel, L.; Kroemer, G. Autophagy and cellular immune responses. Immunity 2013, 39, 211–227. [Google Scholar] [CrossRef]
- Zhan, Z.; Xie, X.; Cao, H.; Zhou, X.; Zhang, X.D.; Fan, H.; Liu, Z. Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. Autophagy 2014, 10, 257–268. [Google Scholar] [CrossRef] [Green Version]
- Tang, D.; Kang, R.; Cheh, C.W.; Livesey, K.M.; Liang, X.; Schapiro, N.E.; Benschop, R.; Sparvero, L.J.; Amoscato, A.A.; Tracey, K.J.; et al. HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 2010, 29, 5299–5310. [Google Scholar] [CrossRef] [PubMed]
- Schmeisser, H.; Fey, S.B.; Horowitz, J.; Fischer, E.R.; Balinsky, C.A.; Miyake, K.; Bekisz, J.; Snow, A.L.; Zoon, K.C. Type I interferons induce autophagy in certain human cancer cell lines. Autophagy 2013, 9, 683–696. [Google Scholar] [CrossRef] [PubMed]
- Kiyono, K.; Suzuki, H.I.; Matsuyama, H.; Morishita, Y.; Komuro, A.; Kano, M.R.; Sugimoto, K.; Miyazono, K. Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells. Cancer Res. 2009, 69, 8844–8852. [Google Scholar] [CrossRef] [PubMed]
- Katheder, N.S.; Khezri, R.; O’Farrell, F.; Schultz, S.W.; Jain, A.; Rahman, M.M.; Schink, K.O.; Theodossiou, T.A.; Johansen, T.; Juhasz, G.; et al. Microenvironmental autophagy promotes tumour growth. Nature 2017, 541, 417–420. [Google Scholar] [CrossRef]
- Zou, W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer 2005, 5, 263–274. [Google Scholar] [CrossRef]
- Semmling, V.; Lukacs-Kornek, V.; Thaiss, C.A.; Quast, T.; Hochheiser, K.; Panzer, U.; Rossjohn, J.; Perlmutter, P.; Cao, J.; Godfrey, D.I.; et al. Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nat. Immunol. 2010, 11, 313–320. [Google Scholar] [CrossRef]
- Li, H.; Li, Y.; Jiao, J.; Hu, H.M. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nat. Nanotechnol. 2011, 6, 645–650. [Google Scholar] [CrossRef]
- Yang, S.; Imamura, Y.; Jenkins, R.W.; Canadas, I.; Kitajima, S.; Aref, A.; Brannon, A.; Oki, E.; Castoreno, A.; Zhu, Z.; et al. Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation. Cancer Immunol. Res. 2016, 4, 520–530. [Google Scholar] [CrossRef]
- Wang, X.; Wu, W.K.K.; Gao, J.; Li, Z.; Dong, B.; Lin, X.; Li, Y.; Li, Y.; Gong, J.; Qi, C.; et al. Autophagy inhibition enhances PD-L1 expression in gastric cancer. J. Exp. Clin. Cancer Res. 2019, 38, 140. [Google Scholar] [CrossRef]
- Deretic, V.; Levine, B. Autophagy balances inflammation in innate immunity. Autophagy 2018, 14, 243–251. [Google Scholar] [CrossRef] [Green Version]
- Mathew, R.; Khor, S.; Hackett, S.R.; Rabinowitz, J.D.; Perlman, D.H.; White, E. Functional role of autophagy-mediated proteome remodeling in cell survival signaling and innate immunity. Mol. Cell 2014, 55, 916–930. [Google Scholar] [CrossRef] [PubMed]
- Poillet-Perez, L.; Sharp, D.W.; Yang, Y.; Laddha, S.V.; Ibrahim, M.; Bommareddy, P.K.; Hu, Z.S.; Vieth, J.; Haas, M.; Bosenberg, M.W.; et al. Autophagy promotes growth of tumors with high mutational burden by inhibiting a T-cell immune response. Nat. Cancer 2020, 1, 923–934. [Google Scholar] [CrossRef] [PubMed]
- Yatim, N.; Cullen, S.; Albert, M.L. Dying cells actively regulate adaptive immune responses. Nat. Rev. Immunol. 2017, 17, 262–275. [Google Scholar] [CrossRef] [PubMed]
- DeVorkin, L.; Pavey, N.; Carleton, G.; Comber, A.; Ho, C.; Lim, J.; McNamara, E.; Huang, H.; Kim, P.; Zacharias, L.G.; et al. Autophagy Regulation of Metabolism Is Required for CD8(+) T Cell Anti-tumor Immunity. Cell Rep. 2019, 27, 502–513.e5. [Google Scholar] [CrossRef] [PubMed]
- Yamamoto, K.; Venida, A.; Yano, J.; Biancur, D.E.; Kakiuchi, M.; Gupta, S.; Sohn, A.S.W.; Mukhopadhyay, S.; Lin, E.Y.; Parker, S.J.; et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature 2020, 581, 100–105. [Google Scholar] [CrossRef]
- Garg, A.D.; Dudek, A.M.; Agostinis, P. Autophagy-dependent suppression of cancer immunogenicity and effector mechanisms of innate and adaptive immunity. Oncoimmunology 2013, 2, e26260. [Google Scholar] [CrossRef]
- Baginska, J.; Viry, E.; Berchem, G.; Poli, A.; Noman, M.Z.; van Moer, K.; Medves, S.; Zimmer, J.; Oudin, A.; Niclou, S.P.; et al. Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia. Proc. Natl. Acad. Sci. USA 2013, 110, 17450–17455. [Google Scholar] [CrossRef]
- Noman, M.Z.; Janji, B.; Kaminska, B.; Van Moer, K.; Pierson, S.; Przanowski, P.; Buart, S.; Berchem, G.; Romero, P.; Mami-Chouaib, F.; et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Res. 2011, 71, 5976–5986. [Google Scholar] [CrossRef]
- Zhong, Z.; Sanchez-Lopez, E.; Karin, M. Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Cell 2016, 166, 288–298. [Google Scholar] [CrossRef]
- Blum, J.S.; Wearsch, P.A.; Cresswell, P. Pathways of antigen processing. Annu. Rev. Immunol. 2013, 31, 443–473. [Google Scholar] [CrossRef] [Green Version]
- Loi, M.; Muller, A.; Steinbach, K.; Niven, J.; Barreira da Silva, R.; Paul, P.; Ligeon, L.A.; Caruso, A.; Albrecht, R.A.; Becker, A.C.; et al. Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses. Cell Rep. 2016, 15, 1076–1087. [Google Scholar] [CrossRef] [PubMed]
- Parekh, V.V.; Pabbisetty, S.K.; Wu, L.; Sebzda, E.; Martinez, J.; Zhang, J.; Van Kaer, L. Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8alpha(+) dendritic cells. Proc. Natl. Acad. Sci. USA 2017, 114, E6371–E6380. [Google Scholar] [CrossRef] [PubMed]
- Zou, W.; Wolchok, J.D.; Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 2016, 8, 328rv324. [Google Scholar] [CrossRef] [PubMed]
- Jang, Y.J.; Kim, J.H.; Byun, S. Modulation of Autophagy for Controlling Immunity. Cells 2019, 8, 138. [Google Scholar] [CrossRef] [PubMed]
- Clarke, A.J.; Simon, A.K. Autophagy in the renewal, differentiation and homeostasis of immune cells. Nat. Rev. Immunol. 2019, 19, 170–183. [Google Scholar] [CrossRef] [PubMed]
- Xia, H.; Wang, W.; Crespo, J.; Kryczek, I.; Li, W.; Wei, S.; Bian, Z.; Maj, T.; He, M.; Liu, R.J.; et al. Suppression of FIP200 and autophagy by tumor-derived lactate promotes naive T cell apoptosis and affects tumor immunity. Sci. Immunol. 2017, 2, eaan4631. [Google Scholar] [CrossRef] [PubMed]
- Sena, L.A.; Li, S.; Jairaman, A.; Prakriya, M.; Ezponda, T.; Hildeman, D.A.; Wang, C.R.; Schumacker, P.T.; Licht, J.D.; Perlman, H.; et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013, 38, 225–236. [Google Scholar] [CrossRef]
- Jia, W.; He, M.X.; McLeod, I.X.; Guo, J.; Ji, D.; He, Y.W. Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1. Autophagy 2015, 11, 2335–2345. [Google Scholar] [CrossRef] [PubMed]
- Bronietzki, A.W.; Schuster, M.; Schmitz, I. Autophagy in T-cell development, activation and differentiation. Immunol. Cell Biol. 2015, 93, 25–34. [Google Scholar] [CrossRef] [PubMed]
- Yang, G.; Song, W.; Postoak, J.L.; Chen, J.; Martinez, J.; Zhang, J.; Wu, L.; Van Kaer, L. Autophagy-related protein PIK3C3/VPS34 controls T cell metabolism and function. Autophagy 2021, 17, 1193–1204. [Google Scholar] [CrossRef]
- Pua, H.H.; Guo, J.; Komatsu, M.; He, Y.W. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J. Immunol. 2009, 182, 4046–4055. [Google Scholar] [CrossRef] [PubMed]
- Swadling, L.; Pallett, L.J.; Diniz, M.O.; Baker, J.M.; Amin, O.E.; Stegmann, K.A.; Burton, A.R.; Schmidt, N.M.; Jeffery-Smith, A.; Zakeri, N.; et al. Human Liver Memory CD8(+) T Cells Use Autophagy for Tissue Residence. Cell Rep. 2020, 30, 687–698.e686. [Google Scholar] [CrossRef] [PubMed]
- Delgoffe, G.M.; Kole, T.P.; Zheng, Y.; Zarek, P.E.; Matthews, K.L.; Xiao, B.; Worley, P.F.; Kozma, S.C.; Powell, J.D. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009, 30, 832–844. [Google Scholar] [CrossRef] [PubMed]
- Le Texier, L.; Lineburg, K.E.; Cao, B.; McDonald-Hyman, C.; Leveque-El Mouttie, L.; Nicholls, J.; Melino, M.; Nalkurthi, B.C.; Alexander, K.A.; Teal, B.; et al. Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease. JCI Insight 2016, 1, e86850. [Google Scholar] [CrossRef]
- Wei, J.; Long, L.; Yang, K.; Guy, C.; Shrestha, S.; Chen, Z.; Wu, C.; Vogel, P.; Neale, G.; Green, D.R.; et al. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nat. Immunol. 2016, 17, 277–285. [Google Scholar] [CrossRef]
- Becher, J.; Simula, L.; Volpe, E.; Procaccini, C.; La Rocca, C.; D’Acunzo, P.; Cianfanelli, V.; Strappazzon, F.; Caruana, I.; Nazio, F.; et al. AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis. Dev. Cell 2018, 47, 592–607.e596. [Google Scholar] [CrossRef]
- Munz, C. Autophagy proteins in antigen processing for presentation on MHC molecules. Immunol. Rev. 2016, 272, 17–27. [Google Scholar] [CrossRef]
- Li, W.; Tanikawa, T.; Kryczek, I.; Xia, H.; Li, G.; Wu, K.; Wei, S.; Zhao, L.; Vatan, L.; Wen, B.; et al. Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer. Cell Metab. 2018, 28, 87–103.e106. [Google Scholar] [CrossRef]
- Parker, K.H.; Horn, L.A.; Ostrand-Rosenberg, S. High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy. J. Leukoc. Biol. 2016, 100, 463–470. [Google Scholar] [CrossRef]
- Alissafi, T.; Hatzioannou, A.; Mintzas, K.; Barouni, R.M.; Banos, A.; Sormendi, S.; Polyzos, A.; Xilouri, M.; Wielockx, B.; Gogas, H.; et al. Autophagy orchestrates the regulatory program of tumor-associated myeloid-derived suppressor cells. J. Clin. Investig. 2018, 128, 3840–3852. [Google Scholar] [CrossRef]
- Pan, H.; Chen, L.; Xu, Y.; Han, W.; Lou, F.; Fei, W.; Liu, S.; Jing, Z.; Sui, X. Autophagy-associated immune responses and cancer immunotherapy. Oncotarget 2016, 7, 21235–21246. [Google Scholar] [CrossRef] [PubMed]
- Arnold, J.; Murera, D.; Arbogast, F.; Fauny, J.D.; Muller, S.; Gros, F. Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses. Cell Death Differ. 2016, 23, 853–864. [Google Scholar] [CrossRef] [PubMed]
- Fribourg, M.; Ni, J.; Nina Papavasiliou, F.; Yue, Z.; Heeger, P.S.; Leventhal, J.S. Allospecific Memory B Cell Responses Are Dependent on Autophagy. Am. J. Transpl. 2018, 18, 102–112. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Xia, P.; Huang, G.; Zhu, P.; Liu, J.; Ye, B.; Du, Y.; Fan, Z. FoxO1-mediated autophagy is required for NK cell development and innate immunity. Nat. Commun. 2016, 7, 11023. [Google Scholar] [CrossRef]
- Salio, M.; Puleston, D.J.; Mathan, T.S.; Shepherd, D.; Stranks, A.J.; Adamopoulou, E.; Veerapen, N.; Besra, G.S.; Hollander, G.A.; Simon, A.K.; et al. Essential role for autophagy during invariant NKT cell development. Proc. Natl. Acad. Sci. USA 2014, 111, E5678–E5687. [Google Scholar] [CrossRef]
- Pei, B.; Zhao, M.; Miller, B.C.; Vela, J.L.; Bruinsma, M.W.; Virgin, H.W.; Kronenberg, M. Invariant NKT cells require autophagy to coordinate proliferation and survival signals during differentiation. J. Immunol. 2015, 194, 5872–5884. [Google Scholar] [CrossRef]
- Liu, E.; Van Grol, J.; Subauste, C.S. Atg5 but not Atg7 in dendritic cells enhances IL-2 and IFN-gamma production by Toxoplasma gondii-reactive CD4+ T cells. Microbes Infect. 2015, 17, 275–284. [Google Scholar] [CrossRef]
- Seto, S.; Tsujimura, K.; Horii, T.; Koide, Y. Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells. PLoS ONE 2013, 8, e86017. [Google Scholar] [CrossRef]
- Lee, H.K.; Mattei, L.M.; Steinberg, B.E.; Alberts, P.; Lee, Y.H.; Chervonsky, A.; Mizushima, N.; Grinstein, S.; Iwasaki, A. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 2010, 32, 227–239. [Google Scholar] [CrossRef]
- Chen, P.; Cescon, M.; Bonaldo, P. Autophagy-mediated regulation of macrophages and its applications for cancer. Autophagy 2014, 10, 192–200. [Google Scholar] [CrossRef]
- Jacquel, A.; Obba, S.; Solary, E.; Auberger, P. Proper macrophagic differentiation requires both autophagy and caspase activation. Autophagy 2012, 8, 1141–1143. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Morgan, M.J.; Chen, K.; Choksi, S.; Liu, Z.G. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood 2012, 119, 2895–2905. [Google Scholar] [CrossRef] [PubMed]
- Liu, K.; Zhao, E.; Ilyas, G.; Lalazar, G.; Lin, Y.; Haseeb, M.; Tanaka, K.E.; Czaja, M.J. Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization. Autophagy 2015, 11, 271–284. [Google Scholar] [CrossRef] [PubMed]
- Li, N.; Qin, J.; Lan, L.; Zhang, H.; Liu, F.; Wu, Z.; Ni, H.; Wang, Y. PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism. Cancer Biol. Ther. 2015, 16, 297–306. [Google Scholar] [CrossRef] [PubMed]
- Khatoon, E.; Parama, D.; Kumar, A.; Alqahtani, M.S.; Abbas, M.; Girisa, S.; Sethi, G.; Kunnumakkara, A.B. Targeting PD-1/PD-L1 axis as new horizon for ovarian cancer therapy. Life Sci. 2022, 306, 120827. [Google Scholar] [CrossRef]
- Robainas, M.; Otano, R.; Bueno, S.; Ait-Oudhia, S. Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy. OncoTargets Ther. 2017, 10, 1803–1807. [Google Scholar] [CrossRef]
- Maher, C.M.; Thomas, J.D.; Haas, D.A.; Longen, C.G.; Oyer, H.M.; Tong, J.Y.; Kim, F.J. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1. Mol. Cancer Res. 2018, 16, 243–255. [Google Scholar] [CrossRef]
- Clark, C.A.; Gupta, H.B.; Curiel, T.J. Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential. Autophagy 2017, 13, 987–988. [Google Scholar] [CrossRef]
- Shukla, S.A.; Bachireddy, P.; Schilling, B.; Galonska, C.; Zhan, Q.; Bango, C.; Langer, R.; Lee, P.C.; Gusenleitner, D.; Keskin, D.B.; et al. Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade. Cell 2018, 173, 624–633.e628. [Google Scholar] [CrossRef]
- Kato, H.; Perl, A. Blockade of Treg Cell Differentiation and Function by the Interleukin-21-Mechanistic Target of Rapamycin Axis Via Suppression of Autophagy in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2018, 70, 427–438. [Google Scholar] [CrossRef] [Green Version]
- Alissafi, T.; Banos, A.; Boon, L.; Sparwasser, T.; Ghigo, A.; Wing, K.; Vassilopoulos, D.; Boumpas, D.; Chavakis, T.; Cadwell, K.; et al. Tregs restrain dendritic cell autophagy to ameliorate autoimmunity. J. Clin. Investig. 2017, 127, 2789–2804. [Google Scholar] [CrossRef] [PubMed]
- Folgiero, V.; Miele, E.; Carai, A.; Ferretti, E.; Alfano, V.; Po, A.; Bertaina, V.; Goffredo, B.M.; Benedetti, M.C.; Camassei, F.D.; et al. IDO1 involvement in mTOR pathway: A molecular mechanism of resistance to mTOR targeting in medulloblastoma. Oncotarget 2016, 7, 52900–52911. [Google Scholar] [CrossRef] [PubMed]
- Metz, R.; Rust, S.; Duhadaway, J.B.; Mautino, M.R.; Munn, D.H.; Vahanian, N.N.; Link, C.J.; Prendergast, G.C. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology 2012, 1, 1460–1468. [Google Scholar] [CrossRef] [PubMed]
- McGaha, T.L. IDO-GCN2 and autophagy in inflammation. Oncotarget 2015, 6, 21771–21772. [Google Scholar] [CrossRef]
- Schauer, I.G.; Zhang, J.; Xing, Z.; Guo, X.; Mercado-Uribe, I.; Sood, A.K.; Huang, P.; Liu, J. Interleukin-1beta promotes ovarian tumorigenesis through a p53/NF-kappaB-mediated inflammatory response in stromal fibroblasts. Neoplasia 2013, 15, 409–420. [Google Scholar] [CrossRef]
- Jiang, S.; Dupont, N.; Castillo, E.F.; Deretic, V. Secretory versus degradative autophagy: Unconventional secretion of inflammatory mediators. J. Innate Immun. 2013, 5, 471–479. [Google Scholar] [CrossRef]
- Peral de Castro, C.; Jones, S.A.; Ni Cheallaigh, C.; Hearnden, C.A.; Williams, L.; Winter, J.; Lavelle, E.C.; Mills, K.H.; Harris, J. Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion. J. Immunol. 2012, 189, 4144–4153. [Google Scholar] [CrossRef]
- Sun, K.; Xu, L.; Jing, Y.; Han, Z.; Chen, X.; Cai, C.; Zhao, P.; Zhao, X.; Yang, L.; Wei, L. Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-kappaB-IL1alpha/beta-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis. Cancer Lett. 2017, 388, 198–207. [Google Scholar] [CrossRef]
- Kang, R.; Tang, D.; Lotze, M.T.; Zeh Iii, H.J. Autophagy is required for IL-2-mediated fibroblast growth. Exp. Cell Res. 2013, 319, 556–565. [Google Scholar] [CrossRef]
- Liang, X.; De Vera, M.E.; Buchser, W.J.; Romo de Vivar Chavez, A.; Loughran, P.; Beer Stolz, D.; Basse, P.; Wang, T.; Van Houten, B.; Zeh, H.J., 3rd; et al. Inhibiting systemic autophagy during interleukin 2 immunotherapy promotes long-term tumor regression. Cancer Res. 2012, 72, 2791–2801. [Google Scholar] [CrossRef] [Green Version]
- Qin, B.; Zhou, Z.; He, J.; Yan, C.; Ding, S. IL-6 Inhibits Starvation-induced Autophagy via the STAT3/Bcl-2 Signaling Pathway. Sci. Rep. 2015, 5, 15701. [Google Scholar] [CrossRef] [PubMed]
- Linnemann, A.K.; Blumer, J.; Marasco, M.R.; Battiola, T.J.; Umhoefer, H.M.; Han, J.Y.; Lamming, D.W.; Davis, D.B. Interleukin 6 protects pancreatic beta cells from apoptosis by stimulation of autophagy. FASEB J. 2017, 31, 4140–4152. [Google Scholar] [CrossRef]
- Santarelli, R.; Gonnella, R.; Di Giovenale, G.; Cuomo, L.; Capobianchi, A.; Granato, M.; Gentile, G.; Faggioni, A.; Cirone, M. STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells. Sci. Rep. 2014, 4, 4241. [Google Scholar] [CrossRef] [PubMed]
- Cho, S.H.; Oh, S.Y.; Lane, A.P.; Lee, J.; Oh, M.H.; Lee, S.; Zheng, T.; Zhu, Z. Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways. PLoS ONE 2014, 9, e103685. [Google Scholar] [CrossRef] [PubMed]
- Qi, G.M.; Jia, L.X.; Li, Y.L.; Li, H.H.; Du, J. Adiponectin suppresses angiotensin II-induced inflammation and cardiac fibrosis through activation of macrophage autophagy. Endocrinology 2014, 155, 2254–2265. [Google Scholar] [CrossRef]
- Schmeisser, H.; Bekisz, J.; Zoon, K.C. New function of type I IFN: Induction of autophagy. J. Interf. Cytokine Res. 2014, 34, 71–78. [Google Scholar] [CrossRef]
- Buchser, W.J.; Laskow, T.C.; Pavlik, P.J.; Lin, H.M.; Lotze, M.T. Cell-mediated autophagy promotes cancer cell survival. Cancer Res. 2012, 72, 2970–2979. [Google Scholar] [CrossRef]
- Matsuzawa, T.; Kim, B.H.; Shenoy, A.R.; Kamitani, S.; Miyake, M.; Macmicking, J.D. IFN-gamma elicits macrophage autophagy via the p38 MAPK signaling pathway. J. Immunol. 2012, 189, 813–818. [Google Scholar] [CrossRef]
- Tu, S.P.; Quante, M.; Bhagat, G.; Takaishi, S.; Cui, G.; Yang, X.D.; Muthuplani, S.; Shibata, W.; Fox, J.G.; Pritchard, D.M.; et al. IFN-gamma inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res. 2011, 71, 4247–4259. [Google Scholar] [CrossRef]
- Hubbard, V.M.; Valdor, R.; Patel, B.; Singh, R.; Cuervo, A.M.; Macian, F. Macroautophagy regulates energy metabolism during effector T cell activation. J. Immunol. 2010, 185, 7349–7357. [Google Scholar] [CrossRef] [Green Version]
- Wilson, E.B.; El-Jawhari, J.J.; Neilson, A.L.; Hall, G.D.; Melcher, A.A.; Meade, J.L.; Cook, G.P. Human tumour immune evasion via TGF-beta blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity. PLoS ONE 2011, 6, e22842. [Google Scholar] [CrossRef] [PubMed]
- Ding, Y.; Kim, S.; Lee, S.Y.; Koo, J.K.; Wang, Z.; Choi, M.E. Autophagy regulates TGF-beta expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction. J. Am. Soc. Nephrol. 2014, 25, 2835–2846. [Google Scholar] [CrossRef]
- Zhang, C.; Zhang, X.; Xu, R.; Huang, B.; Chen, A.J.; Li, C.; Wang, J.; Li, X.G. TGF-beta2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion. J. Exp. Clin. Cancer Res. 2017, 36, 162. [Google Scholar] [CrossRef]
- Suzuki, H.I.; Kiyono, K.; Miyazono, K. Regulation of autophagy by transforming growth factor-beta (TGF-beta) signaling. Autophagy 2010, 6, 645–647. [Google Scholar] [CrossRef]
- Wang, M.X.; Cheng, X.Y.; Jin, M.; Cao, Y.L.; Yang, Y.P.; Wang, J.D.; Li, Q.; Wang, F.; Hu, L.F.; Liu, C.F. TNF compromises lysosome acidification and reduces alpha-synuclein degradation via autophagy in dopaminergic cells. Exp. Neurol. 2015, 271, 112–121. [Google Scholar] [CrossRef] [PubMed]
- Ullio, C.; Brunk, U.T.; Urani, C.; Melchioretto, P.; Bonelli, G.; Baccino, F.M.; Autelli, R. Autophagy of metallothioneins prevents TNF-induced oxidative stress and toxicity in hepatoma cells. Autophagy 2015, 11, 2184–2198. [Google Scholar] [CrossRef] [PubMed]
- Pun, N.T.; Subedi, A.; Kim, M.J.; Park, P.H. Globular Adiponectin Causes Tolerance to LPS-Induced TNF-alpha Expression via Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis. PLoS ONE 2015, 10, e0124636. [Google Scholar] [CrossRef]
- Wang, W.; Green, M.; Choi, J.E.; Gijon, M.; Kennedy, P.D.; Johnson, J.K.; Liao, P.; Lang, X.; Kryczek, I.; Sell, A.; et al. CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 2019, 569, 270–274. [Google Scholar] [CrossRef]
- Hou, W.; Xie, Y.; Song, X.; Sun, X.; Lotze, M.T.; Zeh, H.J., 3rd; Kang, R.; Tang, D. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 2016, 12, 1425–1428. [Google Scholar] [CrossRef]
- Gao, M.; Monian, P.; Pan, Q.; Zhang, W.; Xiang, J.; Jiang, X. Ferroptosis is an autophagic cell death process. Cell Res. 2016, 26, 1021–1032. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.L.; Zhang, H.L.; Huang, Y.; Huang, J.H.; Sun, P.; Zhou, N.N.; Chen, Y.H.; Mai, J.; Wang, Y.; Yu, Y.; et al. Autophagy deficiency promotes triple-negative breast cancer resistance to T cell-mediated cytotoxicity by blocking tenascin-C degradation. Nat. Commun. 2020, 11, 3806. [Google Scholar] [CrossRef] [PubMed]
- Michaud, M.; Martins, I.; Sukkurwala, A.Q.; Adjemian, S.; Ma, Y.; Pellegatti, P.; Shen, S.; Kepp, O.; Scoazec, M.; Mignot, G.; et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011, 334, 1573–1577. [Google Scholar] [CrossRef] [PubMed]
- Ghiringhelli, F.; Apetoh, L.; Tesniere, A.; Aymeric, L.; Ma, Y.; Ortiz, C.; Vermaelen, K.; Panaretakis, T.; Mignot, G.; Ullrich, E.; et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat. Med. 2009, 15, 1170–1178. [Google Scholar] [CrossRef] [PubMed]
- Ko, A.; Kanehisa, A.; Martins, I.; Senovilla, L.; Chargari, C.; Dugue, D.; Marino, G.; Kepp, O.; Michaud, M.; Perfettini, J.L.; et al. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell Death Differ. 2014, 21, 92–99. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Kuang, X.; Liang, L.; Ye, Y.; Zhang, Y.; Li, J.; Ma, F.; Tao, J.; Lei, G.; Zhao, S.; et al. The Beneficial Role of Sunitinib in Tumor Immune Surveillance by Regulating Tumor PD-L1. Adv. Sci. 2021, 8, 2001596. [Google Scholar] [CrossRef]
- Noman, M.Z.; Janji, B.; Berchem, G.; Mami-Chouaib, F.; Chouaib, S. Hypoxia-induced autophagy: A new player in cancer immunotherapy? Autophagy 2012, 8, 704–706. [Google Scholar] [CrossRef]
- Young, T.M.; Reyes, C.; Pasnikowski, E.; Castanaro, C.; Wong, C.; Decker, C.E.; Chiu, J.; Song, H.; Wei, Y.; Bai, Y.; et al. Autophagy protects tumors from T cell-mediated cytotoxicity via inhibition of TNFalpha-induced apoptosis. Sci. Immunol. 2020, 5, eabb9561. [Google Scholar] [CrossRef]
- Lawson, K.A.; Sousa, C.M.; Zhang, X.; Kim, E.; Akthar, R.; Caumanns, J.J.; Yao, Y.; Mikolajewicz, N.; Ross, C.; Brown, K.R.; et al. Functional genomic landscape of cancer-intrinsic evasion of killing by T cells. Nature 2020, 586, 120–126. [Google Scholar] [CrossRef]
- Mulcahy Levy, J.M.; Zahedi, S.; Griesinger, A.M.; Morin, A.; Davies, K.D.; Aisner, D.L.; Kleinschmidt-DeMasters, B.K.; Fitzwalter, B.E.; Goodall, M.L.; Thorburn, J.; et al. Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors. Elife 2017, 6, e19671. [Google Scholar] [CrossRef]
- Bryant, K.L.; Stalnecker, C.A.; Zeitouni, D.; Klomp, J.E.; Peng, S.; Tikunov, A.P.; Gunda, V.; Pierobon, M.; Waters, A.M.; George, S.D.; et al. Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat. Med. 2019, 25, 628–640. [Google Scholar] [CrossRef]
- Kim, S.; Ramakrishnan, R.; Lavilla-Alonso, S.; Chinnaiyan, P.; Rao, N.; Fowler, E.; Heine, J.; Gabrilovich, D.I. Radiation-induced autophagy potentiates immunotherapy of cancer via up-regulation of mannose 6-phosphate receptor on tumor cells in mice. Cancer Immunol. Immunother. 2014, 63, 1009–1021. [Google Scholar] [CrossRef] [PubMed]
- Ramakrishnan, R.; Huang, C.; Cho, H.I.; Lloyd, M.; Johnson, J.; Ren, X.; Altiok, S.; Sullivan, D.; Weber, J.; Celis, E.; et al. Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy. Cancer Res. 2012, 72, 5483–5493. [Google Scholar] [CrossRef] [PubMed]
- Hahn, T.; Akporiaye, E.T. alpha-TEA as a stimulator of tumor autophagy and enhancer of antigen cross-presentation. Autophagy 2013, 9, 429–431. [Google Scholar] [CrossRef] [PubMed]
- Shen, T.; Zhu, W.; Yang, L.; Liu, L.; Jin, R.; Duan, J.; Anderson, J.M.; Ai, H. Lactosylated N-Alkyl polyethylenimine coated iron oxide nanoparticles induced autophagy in mouse dendritic cells. Regen. Biomater. 2018, 5, 141–149. [Google Scholar] [CrossRef]
- Lin, S.Y.; Hsieh, S.Y.; Fan, Y.T.; Wei, W.C.; Hsiao, P.W.; Tsai, D.H.; Wu, T.S.; Yang, N.S. Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance. Autophagy 2018, 14, 778–795. [Google Scholar] [CrossRef]
- Dai, Z.; Huang, J.; Lei, X.; Yan, Y.; Lu, P.; Zhang, H.; Lin, W.; Chen, W.; Ma, J.; Xie, Q. Efficacy of an autophagy-targeted DNA vaccine against avian leukosis virus subgroup J. Vaccine 2017, 35, 808–813. [Google Scholar] [CrossRef]
- Gabai, V.L.; Shifrin, V.I. Feasibility analysis of p62 (SQSTM1)-encoding DNA vaccine as a novel cancer immunotherapy. Int. Rev. Immunol. 2014, 33, 375–382. [Google Scholar] [CrossRef]
- Noman, M.Z.; Parpal, S.; Van Moer, K.; Xiao, M.; Yu, Y.; Viklund, J.; De Milito, A.; Hasmim, M.; Andersson, M.; Amaravadi, R.K.; et al. Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy. Sci. Adv. 2020, 6, eaax7881. [Google Scholar] [CrossRef]
- Sharma, G.; Ojha, R.; Noguera-Ortega, E.; Rebecca, V.W.; Attanasio, J.; Liu, S.; Piao, S.; Lee, J.J.; Nicastri, M.C.; Harper, S.L.; et al. PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma. JCI Insight 2020, 5, e133225. [Google Scholar] [CrossRef]
- Yu, W.; Wang, Y.; Zhu, J.; Jin, L.; Liu, B.; Xia, K.; Wang, J.; Gao, J.; Liang, C.; Tao, H. Autophagy inhibitor enhance ZnPc/BSA nanoparticle induced photodynamic therapy by suppressing PD-L1 expression in osteosarcoma immunotherapy. Biomaterials 2019, 192, 128–139. [Google Scholar] [CrossRef]
- Lotze, M.T.; Buchser, W.J.; Liang, X. Blocking the interleukin 2 (IL2)-induced systemic autophagic syndrome promotes profound antitumor effects and limits toxicity. Autophagy 2012, 8, 1264–1266. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Cai, W.; Yu, J.; Zhou, S.; Li, X.; He, Z.; Ouyang, D.; Liu, H.; Wang, Y. Autophagy inhibition recovers deficient ICD-based cancer immunotherapy. Biomaterials 2022, 287, 121651. [Google Scholar] [CrossRef] [PubMed]
- Rosenfeld, M.R.; Ye, X.; Supko, J.G.; Desideri, S.; Grossman, S.A.; Brem, S.; Mikkelson, T.; Wang, D.; Chang, Y.C.; Hu, J.; et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 2014, 10, 1359–1368. [Google Scholar] [CrossRef] [PubMed]
- Zeh, H.J.; Bahary, N.; Boone, B.A.; Singhi, A.D.; Miller-Ocuin, J.L.; Normolle, D.P.; Zureikat, A.H.; Hogg, M.E.; Bartlett, D.L.; Lee, K.K.; et al. A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients. Clin. Cancer Res. 2020, 26, 3126–3134. [Google Scholar] [CrossRef] [PubMed]
- Gostner, J.M.; Schrocksnadel, S.; Becker, K.; Jenny, M.; Schennach, H.; Uberall, F.; Fuchs, D. Antimalarial drug chloroquine counteracts activation of indoleamine (2,3)-dioxygenase activity in human PBMC. FEBS Open Biol. 2012, 2, 241–245. [Google Scholar] [CrossRef]
- Wu, J.; Zhao, X.; Sun, Q.; Jiang, Y.; Zhang, W.; Luo, J.; Li, Y. Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model. Biomed. Pharmacother. 2020, 125, 109746. [Google Scholar] [CrossRef]
- Newick, K.; O’Brien, S.; Moon, E.; Albelda, S.M. CAR T Cell Therapy for Solid Tumors. Annu. Rev. Med. 2017, 68, 139–152. [Google Scholar] [CrossRef]
- Levy, J.; Cacheux, W.; Bara, M.A.; L’Hermitte, A.; Lepage, P.; Fraudeau, M.; Trentesaux, C.; Lemarchand, J.; Durand, A.; Crain, A.M.; et al. Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nat. Cell Biol. 2015, 17, 1062–1073. [Google Scholar] [CrossRef]
- Li, Y.; Wang, L.X.; Yang, G.; Hao, F.; Urba, W.J.; Hu, H.M. Efficient cross-presentation depends on autophagy in tumor cells. Cancer Res. 2008, 68, 6889–6895. [Google Scholar] [CrossRef]
- Bian, Y.; Li, W.; Kremer, D.M.; Sajjakulnukit, P.; Li, S.; Crespo, J.; Nwosu, Z.C.; Zhang, L.; Czerwonka, A.; Pawlowska, A.; et al. Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature 2020, 585, 277–282. [Google Scholar] [CrossRef]
Autophagy Inhibitor | Targets | Immunotherapy | Tumor Types | Refs. |
---|---|---|---|---|
SB02024 | Vps34 | Anti-PD-L1 and Anti-PD-1 | Melanoma, CRC | [148] |
SAR405 | Vps34 | Anti-PD-L1 and Anti-PD-1 | Melanoma, CRC | [148] |
Autophinib | Vps34 | TNFα | Various cancers | [138] |
Hydroxychloroquine | Lysosomes, PPT1 | anti-PD-1 | Melanoma | [149] |
LipHCQa | Lysosomes | Shikonin-induced ICD | Colon cancer | [152] |
Chloroquine | Lysosomes | anti-PD1/CTLA4 HDIL-2 | Pancreatic cancer, metastatic liver cancer, renal cell carcinoma | [55,110,151] |
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Lei, Y.; Zhang, E.; Bai, L.; Li, Y. Autophagy in Cancer Immunotherapy. Cells 2022, 11, 2996. https://doi.org/10.3390/cells11192996
Lei Y, Zhang E, Bai L, Li Y. Autophagy in Cancer Immunotherapy. Cells. 2022; 11(19):2996. https://doi.org/10.3390/cells11192996
Chicago/Turabian StyleLei, Yuhe, Enxin Zhang, Liangliang Bai, and Yingjie Li. 2022. "Autophagy in Cancer Immunotherapy" Cells 11, no. 19: 2996. https://doi.org/10.3390/cells11192996