Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Fac. de Médecine - Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
Front Immunol. 2023 Jul 20;14:1205984. doi: 10.3389/fimmu.2023.1205984. eCollection 2023.
Tumor-infiltrating lymphocytes (TIL) often include a substantial subset of CD8 tissue-resident memory T (T) cells enriched in tumor-specific T cells. These T cells play a major role in antitumor immune response. They are identified on the basis of their expression of the CD103 (α(CD103)β) and/or CD49a (α(CD49a)β) integrins, and the C-type lectin CD69, which are involved in tissue residency. T cells express several T-cell inhibitory receptors on their surface but they nevertheless react strongly to malignant cells, exerting a strong cytotoxic function, particularly in the context of blocking interactions of PD-1 with PD-L1 on target cells. These T cells form stable conjugates with autologous tumor cells and interact with dendritic cells and other T cells within the tumor microenvironment to orchestrate an optimal T-cell response. There is growing evidence to indicate that TGF-β is essential for the formation and maintenance of T cells in the tumor, through the induction of CD103 expression on activated CD8 T cells, and for the regulation of T effector functions through bidirectional integrin signaling. CD8 T cells were initially described as a prognostic marker for survival in patients with various types of cancer, including ovarian, lung and breast cancers and melanoma. More recently, these tumor-resident CD8 T cells have been shown to be a potent predictive biomarker of the response of cancer patients to immunotherapies, including therapeutic cancer vaccines and immune checkpoint blockade. In this review, we will highlight the major characteristics of tumor T cell populations and the possibilities for their exploitation in the design of more effective immunotherapy strategies for cancer.
肿瘤浸润淋巴细胞（TIL）通常包含大量富含肿瘤特异性 T 细胞的 CD8 组织驻留记忆 T（T）细胞。这些 T 细胞在抗肿瘤免疫反应中发挥主要作用。它们是基于其表达的 CD103（α（CD103）β）和/或 CD49a（α（CD49a）β）整合素以及参与组织驻留的 C 型凝集素 CD69 来识别的。T 细胞在其表面表达几种 T 细胞抑制性受体，但它们仍然强烈地反应恶性细胞，发挥强烈的细胞毒性作用，特别是在阻断 PD-1 与靶细胞上 PD-L1 的相互作用的情况下。这些 T 细胞与自身肿瘤细胞形成稳定的共轭，并与肿瘤微环境中的树突状细胞和其他 T 细胞相互作用，以协调最佳的 T 细胞反应。越来越多的证据表明，TGF-β 通过诱导激活的 CD8 T 细胞上 CD103 的表达，以及通过双向整合素信号调节 T 效应功能，对于 T 细胞在肿瘤中的形成和维持是必不可少的。CD8 T 细胞最初被描述为各种类型癌症（包括卵巢癌、肺癌、乳腺癌和黑色素瘤）患者生存的预后标志物。最近，这些肿瘤驻留的 CD8 T 细胞已被证明是癌症患者对免疫疗法（包括治疗性癌症疫苗和免疫检查点阻断）反应的有力预测生物标志物。在这篇综述中，我们将重点介绍肿瘤 T 细胞群体的主要特征及其在设计更有效的癌症免疫治疗策略中的可能性。
