Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 Accéder directement au contenu
Article Dans Une Revue Cancer Research Année : 2018

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

Résumé

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.

Domaines

Immunité innée

Dates et versions

inserm-02436039 , version 1 (12-01-2020)

Identifiants

Citer

Emmanuel Patin, Daphnée Soulard, Sébastien Fleury, Maya Hassane, David Dombrowicz, et al.. Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer. Cancer Research, 2018, 78 (1), pp.195-204. ⟨10.1158/0008-5472.CAN-17-1416⟩. ⟨inserm-02436039⟩
100 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More