CD8+ T cells can be polarized into several different subsets as defined by the cytokines they produce and the transcription factors that govern their differentiation. Here, we identified the polarizing conditions to induce an IL22-producing CD8+ Tc22 subset, which is dependent on IL6 and the aryl hydrocarbon receptor transcription factor. Further characterization showed that this subset was highly cytolytic and expressed a distinct cytokine profile and transcriptome relative to other subsets. In addition, polarized Tc22 were able to control tumor growth as well as, if not better than, the traditional IFNγ-producing Tc1 subset. Tc22s were also found to infiltrate the tumors of human patients with ovarian cancer, comprising up to approximately 30% of expanded CD8+ tumor-infiltrating lymphocytes (TIL). Importantly, IL22 production in these CD8+ TILs correlated with improved recurrence-free survival. Given the antitumor properties of Tc22 cells, it may be prudent to polarize T cells to the Tc22 lineage when using chimeric antigen receptor (CAR)-T or T-cell receptor (TCR) transduction-based immunotherapies.

中文翻译：

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IL6 诱导具有有效抗肿瘤功能的 IL22+ CD8+ T 细胞亚群。


CD8+ T 细胞可以根据它们产生的细胞因子和控制其分化的转录因子而极化成几个不同的亚群。在这里，我们确定了诱导产生 IL22 的 CD8+ Tc22 子集的极化条件，该子集依赖于 IL6 和芳基烃受体转录因子。进一步的表征表明，该亚群具有高度的细胞溶解性，并且相对于其他亚群表达独特的细胞因子谱和转录组。此外，极化 Tc22 能够控制肿瘤生长，甚至优于传统的产生 IFNγ 的 Tc1 子集。 Tc22 还被发现能浸润人类卵巢癌患者的肿瘤，其中约占 30% 的扩增 CD8+ 肿瘤浸润淋巴细胞 (TIL)。重要的是，这些 CD8+ TIL 中 IL22 的产生与无复发生存率的改善相关。鉴于 Tc22 细胞的抗肿瘤特性，在使用基于嵌合抗原受体 (CAR)-T 或 T 细胞受体 (TCR) 转导的免疫疗法时，将 T 细胞极化为 Tc22 谱系可能是谨慎的做法。