文章基本信息

标题：Tumor-specific IL-9–producing CD8+ Tc9 cells are superior effector than type-I cytotoxic Tc1 cells for adoptive immunotherapy of cancers
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作者：Yong Lu ; Bangxing Hong ; Haiyan Li 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：6
页码：2265-2270
DOI：10.1073/pnas.1317431111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Because cytokine-priming signals direct CD8+ T cells to acquire unique profiles that affect their ability to mediate specific immune responses, here we generated IL-9-skewed CD8+ T (Tc9) cells by priming with Th9-polarized condition. Compared with type-I CD8+ cytotoxic 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-{gamma}- and granzyme-B (GrzB)-producing cytolytic Tc1-like effector cells. Phenotypic analysis revealed that adoptively transferred Tc9 cells secreted IL-2 and were KLRG-1low and IL-7Rhigh, 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 CD8+ T-cell-based adoptive immunotherapy of cancers.
关键词：adoptive cell therapy ; less-exhausted T cells ; T-cell lineage plasticity