"研究通过Th9极化条件诱导生成了IL-9导向的CD8+ T细胞(Tc9)，与Tc1细胞相比，Tc9分泌不同且胞毒性较低，但在晚期肿瘤模型中展现出更强的抗肿瘤效果。Tc9细胞在体内能持久存在并转化为IFN-γ和GrzB表达的效应细胞，表现出"年轻"特征或长寿自更新能力。IL-9在治疗效果中起关键作用，这些发现对癌症的CD8+ T细胞疗法有临床应用潜力。"
摘要：
Because cytokine-priming signals direct CD8T cells to acquire unique profiles that affect their ability to mediate specific immune responses, here we generated IL-9–skewed CD8T (Tc9) cells by priming with Th9-polarized condition. Compared with type-I CD8cytotoxic T (Tc1) cells, Tc9 secreted different cytokines and were less cytolytic in vitro but surprisingly elicited greater antitumor responses against advanced tumors in OT-I/B16-OVA and Pmel-1/B16 melanoma models. After adoptive transfer, Tc9 cells persisted longer and differentiated into IFN-γ– and granzyme-B (GrzB)–producing cytolytic Tc1-like effector cells. Phenotypic analysis revealed that adoptively transferred Tc9 cells secreted IL-2 and were KLRG-1and IL-7Rα, suggesting that they acquired a signature of "younger" phenotype or became long-term lived cells with capacity of self-renewal. Our results also revealed that Tc9-mediated therapeutic effect critically depended on IL-9 production in vivo. These findings have clinical implications for the improvement of CD8T-cell-based adoptive immunotherapy of cancers.
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