Type I interferon activates MHC class I-dressed CD11b+ conventional dendritic cells to promote protective anti-tumor CD8+ T cell immunity

被引：216

作者：

Duong, Ellen ^{[1
,2
]}

Fessenden, Tim B. ^{[1
]}

Lutz, Emi ^{[1
,3
]}

Dinter, Teresa ^{[1
,2
]}

Yim, Leon ^{[1
]}

Blatt, Sarah ^{[1
]}

Bhutkar, Arjun ^{[1
]}

Wittrup, Karl Dane ^{[1
,3
]}

Spranger, Stefani ^{[1
,2
,4
]}

机构：

[1] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Dept Biol Engn, Cambridge, MA USA

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

来源：

IMMUNITY | 2022年 / 55卷 / 02期

关键词：

ANTIGEN-PRESENTING CELLS; TRANSCRIPTION FACTORS; CROSS-PRESENTATION; TUMOR-CELLS; EXPRESSION; RECEPTOR; INNATE; DIFFERENTIATION; RESPONSES; MELANOMA;

D O I：

10.1016/j.immuni.2021.10.020

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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-b 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.

引用

页码：308 / +

页数：26

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