Type I IFN receptor signalling controls IL-7-dependent accumulation and activity of protumoral IL-17A-producing {gamma}{delta}T cells in breast cancer

The protumoral activity of γδT17 cells has recently emerged in a wide variety of solid malignancies including breast cancer. These cells promote tumor growth, angiogenesis, and subsequent metastasis development. However, the factors that regulate the biology of γδT17 cells within the tumor microenvironment are poorly understood. Here we use two experimental models of breast cancer to reinforce the concept that tumor-infiltrating γδT17 cells are endowed with protumoral functions that promote tumor progression and metastasis development. We also demonstrated a critical role for type I interferon signaling in controlling the preferential accumulation of a peculiar subset of γδT17 cells displaying a CD27- CD3bright phenotype in the tumor bed, previously associated with the invariant Vγ6Vδ1+ TCR. This effect was indirect and relied partially on IFNAR1-dependent control of IL-7 secretion, a factor that triggers proliferation and activating functions of deleterious γδT17 cells. Our work identifies a key role of the type I interferon/IL-7 axis in the regulation of intratumoral γδT17 cell functions and in the development of primary breast tumor growth and metastasis.

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