Targeting tumors with IL-10 prevents dendritic cell-mediated CD8+ T cell apoptosis
Cancer cell, 2019•cell.com
Increasing evidence demonstrates that interleukin-10 (IL-10), 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 …
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 …
Summary
Increasing evidence demonstrates that interleukin-10 (IL-10), 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-γ 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.
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