Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy.
Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy.
复制标题
靶向CD8 T细胞免疫的最新进展，以实现更有效的癌症免疫疗法。
DOI：
10.3389/fimmu.2018.00014
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发表时间：
2018
影响因子：
7.3
通讯作者：
Mami-Chouaib F
中科院分区：
文献类型：
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作者：
Durgeau A;Virk Y;Corgnac S;Mami-Chouaib F
癌症治疗的最新进展来自靶向T细胞抑制性受体的新免疫疗法，包括细胞毒性T淋巴细胞相关抗原（CTLA）-4和PD-1。在这种情况下，抗CTLA-4和抗PD-1单克隆抗体已在许多癌症中显示出生存益处，包括黑色素瘤和非小细胞肺癌。表达PD-1的CD 8 + T淋巴细胞似乎在对这些免疫检查点抑制剂（ICI）的应答中发挥主要作用。细胞毒性T淋巴细胞（CTL）通过T细胞受体（TCR）识别癌细胞表面由主要组织相容性复合物I类/β-2-微球蛋白复合物呈递的特异性抗原肽，并通过杀伤靶细胞（主要通过释放含有穿孔素和颗粒酶B的分泌性溶酶体的内容物）来消除恶性细胞。靶细胞上的T细胞粘附分子，特别是淋巴细胞功能相关抗原-1和CD 103整联蛋白，以及它们的同源配体，分别是细胞间粘附分子1和E-钙粘蛋白，参与加强CTL和肿瘤细胞之间的相互作用。肿瘤特异性CTL已从多种癌症患者的肿瘤浸润淋巴细胞和外周血淋巴细胞（PBL）中分离。TCRβ链基因的使用表明，与自体PBL相比，体外鉴定的CTL在肿瘤部位选择性地在体内扩增。此外，功能研究表明，这些CTL介导的人类白细胞抗原I类限制性细胞毒活性对自体肿瘤细胞。其中一些识别由突变基因编码的真正的肿瘤特异性抗原，也称为新抗原，其可能在抗肿瘤CD 8 T细胞免疫中起关键作用。因此，已经显示针对肿瘤新抗原的T淋巴细胞的存在与患者对免疫疗法的应答相关，所述免疫疗法包括ICI、过继细胞转移和基于树突状细胞的疫苗。这些肿瘤特异性突变衍生抗原为开发有效的第二代治疗性癌症疫苗开辟了新的前景。
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B. T-cell adhesion molecules and, in particular, lymphocyte-function-associated antigen-1 and CD103 integrins, and their cognate ligands, respectively, intercellular adhesion molecule 1 and E-cadherin, on target cells, are involved in strengthening the interaction between CTL and tumor cells. Tumor-specific CTL have been isolated from tumor-infiltrating lymphocytes and peripheral blood lymphocytes (PBL) of patients with varied cancers. TCRβ-chain gene usage indicated that CTL identified in vitro selectively expanded in vivo at the tumor site compared to autologous PBL. Moreover, functional studies indicated that these CTL mediate human leukocyte antigen class I-restricted cytotoxic activity toward autologous tumor cells. Several of them recognize truly tumor-specific antigens encoded by mutated genes, also known as neoantigens, which likely play a key role in antitumor CD8 T-cell immunity. Accordingly, it has been shown that the presence of T lymphocytes directed toward tumor neoantigens is associated with patient response to immunotherapies, including ICI, adoptive cell transfer, and dendritic cell-based vaccines. These tumor-specific mutation-derived antigens open up new perspectives for development of effective second-generation therapeutic cancer vaccines.