| First Author | Patin EC | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 1 | Pages | 195-204 |
| PubMed ID | 29070614 | Mgi Jnum | J:253870 |
| Mgi Id | MGI:6110787 | Doi | 10.1158/0008-5472.CAN-17-1416 |
| Citation | Patin EC, et al. (2018) Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing gammadeltaT Cells in Breast Cancer. Cancer Res 78(1):195-204 |
| abstractText | The protumoral activity of gammadeltaT17 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 gammadeltaT17cells within the tumor microenvironment are less well understood. Here, using two experimental models of breast cancer, we reinforced the concept that tumor-infiltrating gammadeltaT17 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 gammadeltaT17 cells displaying a CD27(-) CD3(bright) phenotype (previously associated with the invariant Vgamma6Vdelta1(+) 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 gammadeltaT17 cells. Our work therefore identifies a key role of the type I IFN/IL7 axis in the regulation of intratumoral gammadeltaT17-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. (c)2017 AACR. |
