Immune checkpoint blockade therapy has been effective but still a significant number of cancer patients either do not respond or become resistant to these therapies. We hypothesized that activating innate immune pathway along with adaptive immune pathway will have a better tumor reduction and survival outcome from immunotherapy treatment. Therefore, we injected TLR1/2 ligand intratumorally in combination with intraperitoneal injection of anti-CTLA4 antibody in a mouse model of melanoma. We show that this combination treatment enhanced anti-tumor immune responses both qualitatively and quantitatively, which is dependent on both CD4 and CD8 T cells. Interestingly, Our results further suggested that increased depletion of regulatory T cells in tumor microenvironment could be one of the mechanisms of enhanced efficacy of combination therapy and this efficacy is dependent upon Fcγ receptor IV expression. This study shows modulation of Fcγ receptor IV expression by a TLR ligand on macrophages to be important in efficacy of anti-CTLA4 antibody in a combination therapy and this mechanism could be harnessed to modulate the final outcome of other antibody-based immunomodulatory therapies.
Citation Format: Naveen Sharma, James P. Allison. Fc gamma receptor IV mediated depletionof tumor infiltrating regulatory T cells by anti-CTLA4 antibody is promoted byTLR1/2 agonist and hence its efficacy in anti-tumor combination therapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B143.
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