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Data from Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer

Data from Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer

Authors :
Christophe Paget
François Trottein
Christelle Faveeuw
David Dombrowicz
Maya Hassane
Sébastien Fleury
Daphnée Soulard
Emmanuel C. Patin
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

The protumoral activity of γδT17 cells has recently emerged in a wide variety of solid malignancies, including breast cancer. These cells exert their detrimental functions by promoting tumor growth, angiogenesis, and subsequent metastasis development. However, the intratumoral factors that regulate the biology of γδT17cells within the tumor microenvironment are less well understood. Here, using two experimental models of breast cancer, we reinforced the concept that tumor-infiltrating γδT17 cells are endowed with protumoral functions, which promote tumor progression and metastasis development. More importantly, we demonstrated a critical role for type I IFN signaling in controlling the preferential accumulation in the tumor bed of a peculiar subset of γδT17 cells displaying a CD27− CD3bright phenotype (previously associated with the invariant Vγ6Vδ1+ TCR). Interestingly, this effect was indirect and partially relied on the IFNAR1-dependent control of IL7 secretion, a factor that triggers proliferation and activating functions of deleterious γδT17 cells. Our work therefore identifies a key role of the type I IFN/IL7 axis in the regulation of intratumoral γδT17-cell functions and in the development of primary breast tumor growth and metastasis.Significance: Tumor-derived IL7 can represent a therapeutic target to prevent accumulation of immune cells endowed with potent protumoral activities. Cancer Res; 78(1); 195–204. ©2017 AACR.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....9b8685df85629c14580b0b3292e6a4b9
Full Text :
https://doi.org/10.1158/0008-5472.c.6509906.v1