Self-Maintaining CD103(+) Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses.
Self-Maintaining CD103(+) Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses.
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DOI：
10.1158/2326-6066.cir-19-0554
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发表时间：
2020-02
影响因子：
10.1
通讯作者：
Dong T
中科院分区：
文献类型：
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作者：
Abd Hamid M;Colin-York H;Khalid-Alham N;Browne M;Cerundolo L;Chen JL;Yao X;Rosendo-Machado S;Waugh C;Maldonado-Perez D;Bowes E;Verrill C;Cerundolo V;Conlon CP;Fritzsche M;Peng Y;Dong T
CD 103+肿瘤浸润性T淋巴细胞（TIL）的富集与患者结局的改善相关。然而，人CD 103+细胞毒性CD 8 + T细胞（CTL）的特性及其在肿瘤控制中的作用仍不清楚。本研究通过检测T细胞受体（TCR）匹配的CD 103+和CD 103-肿瘤特异性CTL的体外免疫和体外免疫表型，探讨了CD 103 + CTL的特性和抗肿瘤机制。有趣的是，我们发现分化的CD 103+癌症特异性CTL表达TGFβ1的活性形式，以持续自我调节CD 103的表达，而不依赖于外部的TGFβ1产生细胞。CTL上CD 103的存在改善了TCR抗原敏感性，这使得能够更快地识别癌症和快速的抗肿瘤细胞毒性。这些CD 103 + CTL具有升高的能量潜力和更快的迁移能力。然而，在长时间的癌症暴露后，它们增加了抑制性受体的共表达和升高的T细胞凋亡。我们的数据提供了对成熟的人CD 103+癌症特异性CTL的性质的基本见解，这可能对未来组织定位癌症免疫治疗策略的设计具有重要意义。
Enrichment of CD103+ tumor-infiltrating T lymphocytes (TILs) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTLs) and their role in tumor control remains 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 co-expression 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.