Immunosuppressive role of γδ T cells in cancer: the other side of the coin

Development of cancer is associated with evolution of tumor microenvironment which subverts the immune response for its benefit. The tumor environment promotes the production of proinflammatory cytokines, leading to the accumulation of suppressive cells that inhibit antitumor immunity. In contrast, strong lymphocyte infiltration has been reported to be associated with an antitumor response and improved clinical outcome (1). The prevalence of suppressive or anti-tumor immune cells in the tumor environment determines the course of the disease. T cells expressing γδ T cell receptor (TCR) are one of the vital players in tumor infiltrating lymphocytes (TILs). The functional significance of γδ T cells in the tumor environment is still an enigma. The disparate properties of γδ T cells to recognise antigens in MHC unrestricted manner bestow an advantage to γδ T cells over αβT cells for anti-tumor immunity. γδ T cells specifically respond to the stress-induced MHC class I-related molecules MICA, MICB, and the UL16-binding proteins (ULBP) that are upregulated on malignant or stressed cells (2)