Chikungunya virus infection inhibits B16 melanoma-induced immunosuppression of T cells and macrophages mediated by interleukin 10

Immunosuppression in cancer poses challenges for immunotherapy and highlights the vulnerability of immunocompromised patients to viral infections. This study explored how Chikungunya virus (CHIKV) infection potentially inhibits B16-F10 melanoma-induced immunosuppressive effects on T cells and RAW 264.7 macrophages. We found high expression of CHIKV entry genes in melanoma and other cancers, with B16-F10 cells demonstrating greater susceptibility to CHIKV infection than non-tumorigenic cells. Interestingly, the CHIKV-infected B16-F10 cell culture supernatant (B16-F10-CS) reversed the immunosuppressive effects of uninfected B16-F10-CS on T cells. This reversal was characterised by decreased STAT3 activation and increased MAPK activation in T cells, an effect amplified by interleukin 10 (IL-10) receptor blockade. In RAW 264.7 cells, B16-F10-CS enhanced CHIKV infectivity without triggering activation. However, blocking the IL-10 receptor (IL-10R) in RAW 264.7 reduced CHIKV infection. CHIKV infection and IL-10R blockade synergistically inhibited B16-F10-CS-mediated polarisation of RAW 264.7 cells towards immunosuppressive macrophage. Our findings suggest that CHIKV modulates cancer-induced immunosuppression through IL-10-dependent pathways, providing new insights into viral-cancer interactions. This research may contribute to developing novel antiviral immunotherapies and virotherapies beneficial for cancer patients and immunocompromised individuals.