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Tumor-Reactive Immune Cells Protect Against Metastatic Tumor And Induce Immunoediting Of Indolent But Not Quiescent Tumor Cells, Kyle K. Payne, Rebecca Keim, Laura Graham, Michael O. Idowu, Wen Wan, Xiang-Yang Wang, Amir A. Toor, Harry D. Bear, Masoud H. Manjili

Massey Comprehensive Cancer Center Publications

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25⁺ NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25⁺ NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor …