CD8型
生物
MHC I级
主要组织相容性复合体
MHC II级
细胞毒性T细胞
树突状细胞
干扰素
免疫
免疫学
癌症研究
交叉展示
T细胞
抗原
免疫系统
体外
遗传学
作者
Ellen Duong,Tim Fessenden,Emi A. Lutz,Teresa Dinter,Leon Yim,Sarah E. Blatt,Arjun Bhutkar,K. Dane Wittrup,Stefani Spranger
出处
期刊:Immunity
[Elsevier]
日期:2022-02-01
卷期号:55 (2): 308-323.e9
被引量:132
标识
DOI:10.1016/j.immuni.2021.10.020
摘要
Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8+ T cell responses in Batf3-/- mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b+ conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG+ DCs). ISG+ DC-activated CD8+ T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG+ DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG+ DC state, and activation of MHC class I-dressed ISG+ DCs by exogenous IFN-β rescued anti-tumor immunity against progressor tumors in Batf3-/- mice. The ISG+ DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.
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