CD80
CD40
CD86
过继性细胞移植
生物
癌症研究
细胞生物学
免疫疗法
树突状细胞
CD8型
细胞毒性T细胞
肿瘤微环境
T细胞
免疫学
抗原
免疫系统
体外
生物化学
作者
Takaaki Oba,Toshifumi Hoki,Takayoshi Yamauchi,Tibor Keler,Henry C. Marsh,Xuefang Cao,Fumito Ito
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2020-08-26
卷期号:205 (7): 1867-1877
被引量:30
标识
DOI:10.4049/jimmunol.2000347
摘要
Abstract In vivo expansion of adoptively transferred CD8+ T cells is a critical determinant of successful adoptive T cell therapy. Emerging evidence indicates Batf3-dependent conventional type 1 dendritic cells (cDC1s) rarely found within the tumor myeloid compartment are crucial for effector T cell recruitment to the tumor microenvironment. However, the role of cDC1s in expansion of tumor-specific CD8+ T cells remains unclear. In this article, we addressed the role of cDC1s and their costimulatory molecules, CD40, CD70, and CD80/CD86, in expansion and antitumor efficacy of adoptively transferred in vitro–primed CD8+ T cells recognizing nonmutated tumor-associated self-antigens. We found that TLR/CD40–mediated expansion and antitumor efficacy of adoptively transferred tumor-specific CD8+ T cells were abrogated in Batf3−/− mice. Further mechanistic studies using mixed bone marrow chimeric mice identified that CD40 and CD70 but not CD80/CD86 signaling in cDC1s played a critical role in expansion and antitumor efficacy of adoptively transferred CD8+ T cells. Moreover, induction and activation of cDC1s by administration of FMS-like tyrosine kinase 3 ligand (Flt3L) and TLR/CD40 agonists augmented expansion of adoptively transferred CD8+ T cells, delayed tumor growth, and improved survival. These findings reveal a key role for CD40 and CD70 signaling in cDC1s and have major implications for the design of new vaccination strategies with adoptive T cell therapy.
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