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Human TCRγδ+ T cells represent a novel target for IL‐27 activity

IL‐27 and TCRγδ+ T lymphocytes play critical roles in both innate and adaptive immune responses in health and disease, including infection and tumors. Although the activity of IL‐27 is well characterized in different human immune cells, no information is available on the role of IL‐27 in human TCRγδ+ T lymphocytes. Here, we provide the first evidence that TCRγδ+ T lymphocytes express both gp130 and WSX‐1 chains of IL‐27R, and that IL‐27 may function in TCRγδ+ T cells by (i) inducing STAT1 and STAT3 phosphorylation, (ii) stimulating cytotoxicity against tumor cells through upregulation of cytotoxic granules production, (iii) reducing the release of Th2‐related cytokines, such as IL‐5 and IL‐13, and inducing IFN‐γ production, and (iv) upregulating the expression of CD62L. These results highlighted a novel immunoregulatory property of human IL‐27 that may be relevant in the immune response against tumors. Our results may offer new perspectives for the development of future clinical trials using IL‐27 and TCRγδ+ cells for cancer immunotherapy.