|
|
调节性T细胞介导的免疫逃逸在癌症中研究进展
|
Abstract:
多项研究显示调节性T (Treg)细胞在肿瘤细胞中的高浸润与癌症患者生存率低有关。所以确定Treg细胞中特异性表达并且影响Treg细胞稳态和功能的因子是非常重要的，这样可以了解癌症发病机制和确定治疗的靶点。因此，在肿瘤免疫治疗领域中，找到可以消耗Treg细胞并且控制Treg细胞功能从而去增强抗肿瘤免疫应答的方法是非常重要的。本文将回顾Treg细胞是怎样抑制抗肿瘤免疫应答，并讨论这些机制如何共同允许Treg细胞抑制抗肿瘤免疫应答。
Multiple studies have shown that high infiltration of regulatory T (Treg) cells in tumor cells is associated with low survival in cancer patients. Therefore, it is very important to identify the factors that are specifically expressed in Treg cells and affect the homeostasis and function of Treg cells, so as to understand the pathogenesis of cancer and identify therapeutic targets. Therefore, in the field of tumor immunotherapy, it is very important to find ways to consume Treg cells and control Treg cell function to enhance anti-tumor immune response. This article reviews how Treg cells suppress the anti-tumor immune response and discusses how these mechanisms together allow Treg cells to suppress the anti-tumor immune response.
| [1] | Owen, D.L., Sjaastad, L.E. and Farrar, M.A. (2019) Regulatory T Cell Development in the Thymus. The Journal of Immunology, 203, 2031-2041. https://doi.org/10.4049/jimmunol.1900662 |
| [2] | Kaljanac, M. and Abken, H. (2023) Do Treg Speed Up with CARs? Chimeric Antigen Receptor Treg Engineered to Induce Transplant Tolerance. Transplantation, 107, 74-85. https://doi.org/10.1097/TP.0000000000004316 |
| [3] | Kanamori, M., Nakatsukasa, H., Okada, M., Lu, Q. and Yoshimura, A. (2016) Induced Regulatory T Cells: Their Development, Stability, and Applications. Trends in Immunology, 37, 803-811. https://doi.org/10.1016/j.it.2016.08.012 |
| [4] | Togashi, Y., Shitara, K. and Nishikawa, H. (2019) Regulatory T Cells in Cancer Immunosuppression—Implications for Anticancer Therapy. Nature Reviews Clinical Oncology, 16, 356-371. https://doi.org/10.1038/s41571-019-0175-7 |
| [5] | Tanaka, A. and Sakaguchi, S. (2017) Regulatory T Cells in Cancer Immunotherapy. Cell Research, 27, 109-118. https://doi.org/10.1038/cr.2016.151 |
| [6] | Okeke, E.B. and Uzonna, J.E. (2019) The Pivotal Role of Regulatory T Cells in the Regulation of Innate Immune Cells. Frontiers in Immunology, 10, Article 680. https://doi.org/10.3389/fimmu.2019.00680 |
| [7] | Tanaka, A. and Sakaguchi, S. (2019) Targeting Treg Cells in Cancer Immunotherapy. European Journal of Immunology, 49, 1140-1146. https://doi.org/10.1002/eji.201847659 |
| [8] | Kim, G.R. and Choi, J.M. (2022) Current Understanding of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Signaling in T-Cell Biology and Disease Therapy. Molecular Cell, 45, 513-521. https://doi.org/10.14348/molcells.2022.2056 |
| [9] | Liu, Y. and Zheng, P. (2020) Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy. Trends in Pharmacological Sciences, 41, 4-12. https://doi.org/10.1016/j.tips.2019.11.003 |
| [10] | Guo, X.J., Lu, J.C., Zeng, H.Y., et al. (2021) CTLA-4 Synergizes with PD1/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma. Frontiers in Immunology, 12, Article 705378. |
| [11] | Rastogi, I., Jeon, D., Moseman, J.E., Muralidhar, A., Potluri, H.K. and McNeel, D.G. (2022) Role of B Cells as Antigen Presenting Cells. Frontiers in Immunology, 13, Article 954936. https://doi.org/10.3389/fimmu.2022.954936 |
| [12] | Harris, F., Berdugo, Y.A. and Tree, T. (2023) IL-2-Based Approaches to Treg Enhancement. Clinical and Experimental Immunology, 211, 149-163. https://doi.org/10.1093/cei/uxac105 |
| [13] | ？ledzińska, A., Vila de Mucha, M., Bergerhoff, K., et al. (2020) Regulatory T Cells Restrain Interleukin-2-and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells. Immunity, 52, 151-166.e6. |
| [14] | Kuan, R., Agrawal, D.K. and Thankam, F.G. (2021) Treg Cells in Atherosclerosis. Molecular Biology Reports, 48, 4897-4910. https://doi.org/10.1007/s11033-021-06483-x |
| [15] | Aran, A., Garrigós, L., Curigliano, G., Cortés, J. and Martí, M. (2022) Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality. Cancers, 14, Article 1771. https://doi.org/10.3390/cancers14071771 |
| [16] | Takahashi, T., Kuniyasu, Y., Toda, M., et al. (1998) Immunologic Self-Tolerance Maintained by CD25+CD4+ Naturally Anergic and Suppressive T Cells: Induction of Autoimmune Disease by Breaking Their Anergic/Suppressive State. International Immunology, 10, 1969-1980. https://doi.org/10.1093/intimm/10.12.1969 |
| [17] | Liu, Z., Gerner, M.Y., Van Panhuys, N., Levine, A.G., Rudensky, A.Y. and Germain, R.N. (2015) Immune Homeostasis Enforced by Co-Localized Effector and Regulatory T Cells. Nature, 528, 225-230. https://doi.org/10.1038/nature16169 |
| [18] | Scott, E.N., Gocher, A.M., Workman, C.J. and Vignali, D. (2021) Regulatory T Cells: Barriers of Immune Infiltration into the Tumor Microenvironment. Frontiers in Immunology, 12, Article 702726. https://doi.org/10.3389/fimmu.2021.702726 |
| [19] | Solis-Castillo, L.A., Garcia-Romo, G.S., Diaz-Rodriguez, A., et al. (2020) Tumor-Infiltrating Regulatory T Cells, CD8/Treg Ratio, and Cancer Stem Cells Are Correlated with Lymph Node Metastasis in Patients with Early Breast Cancer. Breast Cancer, 27, 837-849. https://doi.org/10.1007/s12282-020-01079-y |
| [20] | De Simone, M., Arrigoni, A., Rossetti, G., et al. (2016) Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells. Immunity, 45, 1135-1147. https://doi.org/10.1016/j.immuni.2016.10.021 |
| [21] | Li, C., Jiang, P., Wei, S., Xu, X. and Wang, J. (2020) Regulatory T Cells in Tumor Microenvironment: New Mechanisms, Potential Therapeutic Strategies and Future Prospects. Molecular Cancer, 19, Article No. 116. https://doi.org/10.1186/s12943-020-01234-1 |
| [22] | Ohue, Y. and Nishikawa, H. (2019) Regulatory T (Treg) Cells in Cancer: Can Treg Cells Be a New Therapeutic Target. Cancer Science, 110, 2080-2089. https://doi.org/10.1111/cas.14069 |
| [23] | Fantini, M.C., Favale, A., Onali, S. and Facciotti, F. (2020) Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf. International Journal of Molecular Sciences, 21, Article 6744. |
| [24] | Saito, T., Nishikawa, H., Wada, H., et al. (2016) Two FOXP3+CD4+ T Cell Subpopulations Distinctly Control the Prognosis of Colorectal Cancers. Nature Medicine, 22, 679-684. https://doi.org/10.1038/nm.4086 |
| [25] | Bose, S., Panda, A.K., Mukherjee, S. and Sa, G. (2015) Curcumin and Tumor Immune-Editing: Resurrecting the Immune System. Cell Division, 10, Article No. 6. |
| [26] | Lei, X., Lei, Y., Li, J.K., et al. (2020) Immune Cells within the Tumor Microenvironment: Biological Functions and Roles in Cancer Immuneotherapy. Cancer Letters, 470, 126-133. https://doi.org/10.1016/j.canlet.2019.11.009 |
| [27] | Schreiber, R.D., Old, L.J. and Smyth, M.J. (2011) Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion. Science, 331, 1565-1570. https://doi.org/10.1126/science.1203486 |
| [28] | Wu, Q., Wu, W., Franca, T., Jacevic, V., Wang, X. and Kuca, K. (2018) Immune Evasion, a Potential Mechanism of Trichothecenes: New Insights into Negative Immune Regulations. International Journal of Molecular Sciences, 19, Article 3307. https://doi.org/10.3390/ijms19113307 |
| [29] | Wu, Q., Wu, W., Fu, B., Shi, L., Wang, X. and Kuca, K. (2019) JNK Signaling in Cancer Cell Survival. Medicinal Research Reviews, 39, 2082-2104. https://doi.org/10.1002/med.21574 |
| [30] | Jiang, X., Wang, J., Deng, X., et al. (2019) Role of the Tumor Microenvironment in PD-L1/PD-1-Mediated Tumor Immune Escape. Molecular Cancer, 18, Article No. 10. https://doi.org/10.1186/s12943-018-0928-4 |
| [31] | Martinez-Bosch, N., Vinaixa, J. and Navarro, P. (2018) Immune Evasion in Pancreatic Cancer: From Mechanisms to Therapy. Cancers, 10, Article 6. https://doi.org/10.3390/cancers10010006 |
| [32] | Barsoum, I.B., Koti, M., Siemens, D.R. and Graham, C.H. (2014) Mechanisms of Hypoxia-Mediated Immune Escape in Cancer. Cancer Research, 74, 7185-7190. https://doi.org/10.1158/0008-5472.CAN-14-2598 |
| [33] | Gil Del Alcazar, C.R., Ale？kovi？, M. and Polyak, K. (2020) Immune Escape during Breast Tumor Progression. Cancer Immunology Research, 8, 422-427. https://doi.org/10.1158/2326-6066.CIR-19-0786 |
| [34] | Raimondo, S., Pucci, M., Alessandro, R. and Fontana, S. (2020) Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives. International Journal of Molecular Sciences, 21, Article 2286. https://doi.org/10.3390/ijms21072286 |
| [35] | Kumagai, S., Togashi, Y., Kamada, T., et al. (2020) The PD-1 Expression Balance between Effector and Regulatory T Cells Predicts the Clinical Efficacy of PD-1 Blockade Therapies. Nature Immunology, 21, 1346-1358. https://doi.org/10.1038/s41590-020-0769-3 |
| [36] | Jia, X., Yan, B., Tian, X., et al. (2021) CD47/SIRPα Pathway Mediates Cancer Immune Escape and Immunotherapy. International Journal of Biological Sciences, 17, 3281-3287. https://doi.org/10.7150/ijbs.60782 |
| [37] | Willingham, S.B., Volkmer, J.P., Gentles, A.J., et al. (2012) The CD47-Signal Regulatory Protein Alpha (SIRPa) Interaction is a Therapeutic Target for Human Solid Tumors. Proceedings of the National Academy of Sciences of the United States of America, 109, 6662-6667. https://doi.org/10.1073/pnas.1121623109 |
| [38] | Wu, Q., You, L., Nepovimova, E., et al. (2022) Hypoxia-Inducible Factors: Master Regulators of Hypoxic Tumor Immune Escape. Journal of Hematology & Oncology, 15, Article No. 77. https://doi.org/10.1186/s13045-022-01292-6 |
| [39] | Vito, A., El-Sayes, N. and Mossman, K. (2020) Hypoxia-Driven Immune Escape in the Tumor Microenvironment. Cells, 9, Article 992. https://doi.org/10.3390/cells9040992 |
| [40] | Liikanen, I., Lauhan, C., Quon, S., et al. (2021) Hypoxia-Inducible Factor Activity Promotes Antitumor Effector Function and Tissue Residency by CD8+ T Cells. Journal of Clinical Investigation, 131, e143729. |
| [41] | Zhang, H., Lu, H., Xiang, L., et al. (2015) HIF-1 Regulates CD47 Expression in Breast Cancer Cells to Promote Evasion of Phagocytosis and Maintenance of Cancer Stem Cells. Proceedings of the National Academy of Sciences of the United States of America, 112, E6215-E6223. https://doi.org/10.1073/pnas.1520032112 |
| [42] | Bao, X., Zhang, J., Huang, G., et al. (2021) The Crosstalk between HIFs and Mitochondrial Dysfunctions in Cancer Development. Cell Death & Disease, 12, Article No. 215. https://doi.org/10.1038/s41419-021-03505-1 |
| [43] | Wang, D., Yang, L., Yu, W., et al. (2019) Colorectal Cancer Cell-Derived CCL20 Recruits Regulatory T Cells to Promote Chemoresistance via FOXO1/CEBPB/NF-κB Signaling. Journal for ImmunoTherapy of Cancer, 7, Article 215. https://doi.org/10.1186/s40425-019-0701-2 |
