Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Enrichment of CD103 tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 cytotoxic CD8 T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 CTLs by assessing T-cell receptor (TCR)-matched CD103 and CD103 cancer-specific CTL immunity and its immunophenotype Interestingly, we found that differentiated CD103 cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.