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Abstract B09: TLR1/2 ligand promotes Fc gamma RIV mediated depletion of tumor-infiltrating treg by anti-CTLA-4 antibody and its anti-tumor efficacy

Many cancer patients either do not respond or become resistant to immunotherapy with checkpoint inhibitors. To determine whether activating both the innate and adaptive immune pathways improve the tumor reduction and survival outcomes achieved with immunotherapy, we treated a mouse model of melanoma with intratumoral injections of TLR1/2 ligand plus intraperitoneal injections of anti-CTLA-4 antibody. This combination treatment enhanced antitumor immune responses both qualitatively and quantitatively, and its efficacy depended on CD4 T cells, CD8 T cells, Fc gamma receptor IV and macrophages. Interestingly, our results suggest a unique and novel mechanism by which TLR1/2 ligand enhances the anti-tumor efficacy of anti-CTLA-4 antibody by increasing Fc gamma receptor IV expression on macrophages and increasing the density of these macrophages in tumor, which in turn enhances the depletion of tumor-infiltrating regulatory T cells. This mechanism could be harnessed to modulate the clinical outcome of other antibody-based immunotherapies. Citation Format: Naveen Sharma, James P. Allison. TLR1/2 ligand promotes Fc gamma RIV mediated depletion of tumor-infiltrating treg by anti-CTLA-4 antibody and its anti-tumor efficacy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B09.