Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis

Increasing evidence demonstrates that interleukin-10 (IL-1 0), known as an immunosuppressive cytokine, induces antitumor effects depending on CD8(+) T cells. However, it remains elusive how immunosuppressive effects of IL-10 contribute to CD8(+) T cell-mediated antitumor immunity. We generated Cetuximab-based IL-10 fusion protein (CmAb-(IL10)(2)) to prolong its half-life and allow tumor-targeted delivery of IL-10. Our results demonstrated potent antitumor effects of CmAb-(IL10)(2) with reduced toxicity. Moreover, we revealed a mechanism of CmAb-(IL10)(2) preventing dendritic cell (DC)-mediated CD8(+) tumor-infiltrating lymphocyte apoptosis through regulating IFN-gamma production. When combined with immune checkpoint blockade, CmAb-(IL10)(2) significantly improves antitumor effects in mice with advanced tumors. Our findings reveal a DC-regulating role of IL-10 to potentiate CD8(+) T cell-mediated antitumor immunity and provide a potential strategy to improve cancer immunotherapy.