D3.350 - Monocytic myeloid-derived suppressor cells (M-MDSCs) increase the expression of TIGIT on γδ T cells

Monocytic myeloid-derived suppressor cells (M-MDSCs) are critical regulators of immune responses, with a capacity for suppressing T cell activity and shaping the tumour microenvironment. γδ T cells, a subset of T lymphocytes, play pivotal roles in anti-tumour immunity, but their function is affected by the immunosuppressive environment of cancer. The overall fitness of γδ T can be increased in vitro by additional vitamin C. This study investigates the impact of MDSCs on γδ T cells. Additionally, we examined whether vitamin C influences M-MDSC function by assessing its effect on key immunosuppressive markers.

γδ T cells were co-cultured with autologous M-MDSCs for 48h at a 1:1 ratio. Flow cytometry was used to assess the expression of inhibitory (TIGIT, PD-1) and activating (NKp30, CD226) receptors on γδ T cells. Cytokines (IL-10, IL-4, IL-6, TNF-α, and IL-17A) and cytotoxic effector molecules (granzyme A, granzyme B, granulysin, and perforin) were quantified using the LEGENDplex multiplex bead-based immunoassay. To assess whether vitamin C influences M-MDSC function, M-MDSCs were incubated with vitamin C, and IL-10, TGF-β, and PD-L1 expression levels were evaluated.

MDSCs significantly upregulated TIGIT expression on γδ T cells (p < 0.05), while changes in PD-1, NKp30, and CD226 expression were not statistically significant. Functionally, MDSCs altered the cytokine milieu by increasing IL-10 and IL-4 production, though these differences did not reach statistical significance. Additionally, transcription factors associated with γδ T cell differentiation, such as RORC and TBX21, remained unchanged. Regarding cytotoxicity, MDSC exposure led to a trend of reduced granzyme B and perforin levels, suggesting a potential suppression of γδ T cell-mediated cytotoxicity. When M-MDSCs were incubated with vitamin C, there were no significant changes in IL-10, TGF-β, or PD-L1 expression.

Our findings indicate that MDSCs exert immunosuppressive effects on γδ T cells by modulating inhibitory receptor expression and altering cytokine secretion profiles. The upregulation of TIGIT suggests an immunoregulatory axis that may contribute to γδ T cell dysfunction in the presence of MDSCs. Further studies are needed to explore alternative strategies for overcoming MDSC-mediated immunosuppression while enhancing γδ T cell function in the tumour microenvironment.