The immunosuppressive tumor microenvironment is a major hurdle to overcome in the development of successful cancer therapies. Newly discovered tissue resident memory CD8+ T cells (TRM) function to create a potent immunostimulatory environment to protect against local reinfection. As TRM are present in abundance in nearly every tissue and can be triggered by cognate peptide alone, without adjuvant, we tested whether we could hijack infection-specific TRM in tumors to reverse the immunosuppressive tumor microenvironment and enhance existing immunotherapies. Mice with established vesicular stomatitis virus (VSV)-specific skin TRM were challenged with the transplantable B16 melanoma cell line. We find VSV-specific CD8+ T cells within established tumors and within 12 hours of cognate peptide delivery, these cells upregulate IFNγ, CD25, and Granzyme B. This led to 1) tumor NK cell activation through Granzyme B upregulation, 2) NK cell recruitment to the tumor, and 3) CD8+ T cell recruitment to the tumor. Ongoing studies are testing whether TRM immunotherapy synergizes with CAR T cell and checkpoint blockade immunotherapies for eradication of recalcitrant tumors. These results demonstrate proof of principal efficacy for exploiting infection-specific TRM as a tumor immunotherapy.
Citation Format: Pamela C. Rosato, Luke S. Manlove, Christine E. Nelson, Christopher A. Pennell, Vaiva Vezys, David Masopust. Harnessing tissue resident memory T cells to combat solid tumors [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 B056.
- ©2016 American Association for Cancer Research.