Consequences of the perivascular niche remodeling for tumoricidal T-cell trafficking into metastasis of ovarian cancer.

Abstract

The treatment-induced activation level within the perivascular tumor microenvironment (TME) that supports T-cell trafficking and optimal T-cell differentiation is unknown. We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy. Analyses of the perivascular TME by spatially resolved omics technologies revealed reduced immunosuppression and increased tumoricidal T-cell trafficking and function after moderate inflammatory responses driven by a CXCR4 antagonist-armed oncolytic virus. Neither weak nor high inflammation created a permissive TME for T-cell trafficking. Notably, treatment-mediated differences in T-cell effector programs acquired within the perivascular TME contrasted with comparable antigenic priming in the tumor-draining lymph nodes regardless of the activation mode of antigen-presenting cells. These findings provide new insights into combinatorial treatment strategies that enable tumor-specific T cells to overcome multiple barriers for enhanced trafficking and control of tumor growth. .