肿瘤免疫疗法已成为肿瘤治疗的重要手段，是肿瘤研究领域的焦点和热点。肿瘤免疫治疗相关药物相继问世，而2018年度诺贝尔生理学或医学奖授予两位在肿瘤免疫治疗中有突出贡献的免疫学家，更是确立了肿瘤免疫治疗时代的到来。本文概述了2018年肿瘤免疫治疗研究的热点及进展，包括新的肿瘤免疫检查点的发现、T细胞耗竭的深入探究、新的肿瘤免疫抑制细胞亚群的发现以及肿瘤免疫治疗新策略的探索。
Tumor immunotherapy has become a first line option for cancer treatment, a hot field in cancer research and a weapon to overcome cancer in the future. A series of tumor immunotherapeutic drugs have been approved and used in clinic. Also the Nobel Prize in Physiology or Medicine in 2018 was awarded to two immunologists who had made outstanding contributions to tumor immunotherapy, revealing the coming of immunotherapy age. This article outlines the hotspots and advances of tumor immunology and immunotherapy in 2018, including the discovery of new immune checkpoints, in-depth understanding of T cell exhaustion, discovery of new tumor immunosuppressive cell subsets, and exploration of new strategies for tumor immunotherapy. These studies will further promote the development of tumor immunotherapy and bring more effective treatments to cancer patients.
[1] Dougan M, Dranoff G. Immune therapy for cancer[J]. Annual Review of Immunology. 2009, 27:83-117.
[2] Burnet M. Cancer-A biological approach[J]. British Medical Journal, 1957, 1(5023):841-847.
[3] Steinman R M. Decisions about dendritic cells:Past, present, and future[J]. Annual Review of Immunology, 2012, 30(1):1-22.
[4] Wang J, Sanmamed M F, Datar I, et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3[J]. Cell, 2018, doi:10.1016/j.cell.2018.11.010.
[5] Zhang Q, Bi J C, Zheng X D, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity[J]. Nature Immunology, 2018, 19(7):723-732.
[6] Chihara N, Madi A, Kondo T, et al. Induction and transcriptional regulation of the co-inhibitory gene module in T cells[J]. Nature, 2018, 558(7710):454-459.
[7] Simoni Y, Becht E, Fehlings M, et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates[J]. Nature, 2018, 557(7706):575-579.
[8] Scheper W, Kelderman S, Fanchi L F, et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers[J]. Nature Medicine, 2018, doi:10.1038/s41591-018-0266-5.
[9] Han Y M, Liu Q Y, Hou J, et al. Tumor-induced generation of splenic erythroblast-like Ter-cells promotes tumor progression[J]. Cell, 2018, 173(3):634-648.
[10] Zhao L T, He R, Long H X, et al. Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells[J]. Nature Medicine, 2018, 24(10):1536-1544.
[11] Liu Y Y, Liang X Y, Yin X N, et al. Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells[J]. Nature Communications, 2017, 8:15207.
[12] Liu Y Y, Lv J D, Liu J Y, et al. STAT3/p53 pathway activation disrupts IFN-β-induced dormancy in tumor-repopulating cells[J]. The Journal of Clinical Investigation, 2018, 128(3):1057-1073.
[13] Liu Y Y, Lv J D, Liang X Y, et al. 3D fibrin stiffness mediates dormancy of tumor-repopulating cells via a Cdc42-driven Tet2 epigenetic program[J]. Cancer Research, 2018, 78(14):3926-3937.
[14] Liu Y Y, Liang X Y, Dong W Q, et al. Tumor repopulating cells induce PD-1 expression in CD8+ T cells by transferring kynurenine and AhR activation[J]. Cancer Cell, 2018, 33(3):480-494.
