Recombinant Listeria promotes tumor rejection by CD8⁺ T cell-dependent remodeling of the tumor microenvironment.

ABSTRACT: Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1⁺PD1^loCD62L^- CD8⁺ T cells. These IFNγ-producing effector CD8⁺ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to

SUBMITTER: Deng W 

PROVIDER: S-EPMC6094133 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature