Attenuated Listeria monocytogenes reprograms M2-polarized tumor-associated macrophages in ovarian cancer leading to iNOS-mediated tumor cell lysis.

ABSTRACT: A principal mechanism by which tumors evade immune-mediated elimination is through immunosuppression. Previous approaches to tumor immunotherapy have focused on modifying the immunosuppressive environment with immune checkpoint inhibitors, cytokine therapy, and other modalities with the intent to generate T-cell based anti-tumor immunity. We hypothesized that transformation of the suppressive ovarian cancer microenvironment could be achieved by introduction of the attenuated ΔactA/ΔinlB strain of Listeria monocytogenes. ΔactA/ΔinlB introduced into the microenvironment of the aggressive ID8-Defb29/Vegf-A murine ovarian carcinoma is preferentially phagocytosed by tumor-associated macrophages (TAMs) and reprograms that population from one of suppression to immunostimulation. TAMs in the perit

SUBMITTER: Lizotte PH 

PROVIDER: S-EPMC4106169 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature