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.
Keywords: B16-F10; B16-F10 cell culture supernatant (B16-F10-CS); Chikungunya virus (CHIKV); Immunosuppression; Interleukin-10 (IL-10); RAW 264.7 macrophages; T cells; Tumour microenvironnement.
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