Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis
Jian Qiao1, Zhida Liu1, Chunbo Dong1
1The Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Abstract:
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.
Related Concept Videos
Neurons: The Cell Body and the Dendrites
Apoptosis
Cell-mediated Immune Responses
Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...


