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 in vitro and its immunophenotype ex vivo . 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.

中文翻译：

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自我维持的CD103 ⁺癌症特异性T细胞具有高能量，具有快速的细胞毒性和效应反应

CD103 +肿瘤浸润性T淋巴细胞（TIL）的富集与患者预后改善有关。但是，人类CD103 +细胞毒性CD8 + T细胞（CTL）的特征及其在肿瘤控制中的作用仍不清楚。我们通过评估T细胞受体（TCR）匹配的CD103 +和CD103-癌特异性CTL免疫力及其离体免疫表型，研究了CD103 + CTL的特征和抗肿瘤机制。有趣的是，我们发现分化的CD103 +癌症特异性CTL表达了TGFβ1的活性形式，可以持续自我调节CD103的表达，而不依赖于外部产生TGFβ1的细胞。CTL上CD103的存在改善了TCR抗原敏感性，从而使更快的癌症识别和快速的抗肿瘤细胞毒性成为可能。这些CD103 + CTL具有更高的能量潜能和更快的迁移能力。然而，在长时间的癌症暴露后，它们的抑制性受体共表达增加，T细胞凋亡增加。我们的数据为成熟的人类CD103 +癌症特异性CTL的性质提供了基本的见识，这可能对未来组织定位的癌症免疫疗法策略的设计具有重要意义。