Tumor-resident Memory T Cells As a Biomarker of the Response to Cancer Immunotherapy

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.