Reprograming responsiveness of tolerogenic CD8+ T cells using a CXCR4 antagonist-armed oncolytic virus requires reversal of M2 macrophage polarization

Overcoming barriers to the generation of antitumor immunity to self-and neo-antigens is a central concern of cancer immunotherapy. This study investigated the effect of interactions between ovarian cancer (OC) cells and the tumor microenvironment (TME) on the ability of oncolytic virotherapy to activate responsiveness of self antigen-specific and neoantigen-specific CD8+ T lymphocytes in tolerogenic and wild-type (WT) murine tumor models, respectively Overall design: The expansion of self antigen-specific CD8+ T cells using a CXCR4 antagonist-expressing oncolytic vaccinia virus (OV) was investigated using transplantable SV40 T antigen (TAg)-positive MOVCAR 5009 OC cells grown orthotopically in non-tumor prone syngeneic TgMISIIR-TAg-Low transgenic (Tag) mice expressing TAg as a self-antigen. MOVCAR 5009-challenged in WT mice served as a model for studying responses to a tumor-expressed neoantigen. Using immunostaining and single-cell RNA sequencing (scRNAseq) analyses, we compared phenotypic and transcriptomic changes in the TME during the induction of CD8+ T cells by OV in Tag mice to those in MOVCAR 5009-challenged WT mice. CMO assignments: CMO301 WT_C CMO302 WT_OV CMO303 Tag_C CMO304 Tag_OV