肿瘤驻留记忆 T 细胞作为肿瘤免疫治疗应答的生物标志物

Tumor-infiltrating lymphocytes (TIL) often include a substantial subset of CD8 + tissue-resident memory T (T RM ) cells enriched in tumor-specific T cells. These T RM cells play a major role in antitumor immune response. They are identified on the basis of their expression of the CD103 ( E (CD103) 7 ) and/or CD49a ( 1 (CD49a) 1 ) integrins, and the C-type lectin CD69, which are involved in tissue residency. T RM 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 RM 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 in situ T-cell response.

There is growing evidence to indicate that TGF- is essential for the formation and maintenance of T RM cells in the tumor, through the induction of CD103 expression on activated CD8 + T cells, and for the regulation of T RM effector functions through bidirectional integrin signaling. CD8 + T RM 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 RM cell populations and the possibilities for their exploitation in the design of more effective immunotherapy strategies for cancer.