Abstract 184: M1-like macrophage infiltration, CD8+ T cell activation, and increased cancer cell apoptosis in immunologically cold Lewis lung carcinoma treated with tumor-trophic Salmonella Typhimurium expressing anticancer proteins in immunocompetent C57BL/6 mice

Abstract

Abstract Immunotherapy has revolutionized cancer treatment with Immune checkpoint inhibitors (ICIs) and genetically engineered T-Cells expressing chimeric antigen receptors (CARs). CAR-T treatment of hematologic malignancies has achieved outstanding patient response rate. CAR T therapy, however, is thwarted in solid tumor treatment due to two major factors: the immune-suppressive tumor microenvironment that Inhibits T-cell infiltration and T-cell function. In addition, cancer resistance to ICIs treatment also limits the solid tumor response rate. This research aims to activate proinflammatory anticancer immune responses in immunologically cold solid tumors using the genetically engineered Salmonella typhimurium VNP20009 strains that express anticancer proteins. Previously, we have shown that the Salmonella Typhimurium VNP20009 strain expressing methioninase (METase) and/or Tumor Necrosis Factor (TNFα) caused rapid tumor destruction of cold Lewis Lung Carcinoma (LLC) grown on immunocompetent C57BL/6 mice. In this investigation, several mechanisms of this tumor tropic anti-cancer bacteria were studied including the innate and adaptive immune system responses and cancer cell apoptosis. In a pilot study, we selected eight tumor tissues treated with several different bacteria strains and performed histological analysis to observe the effectiveness of each. We found that in the tumor tissues treated with VNP20009_rMETase_TNFα, there was infiltration and activation of CD8+ T cells coupled with reduced amounts of T regulatory cells, as well as an increased ratio of M1-like to M2-like macrophages. We also observed increased tumor apoptosis associated with an elevated detection of an apoptosis biomarker and a suppressed amount of the Ki67 tumor growth signal. These findings indicate that VNP20009_rMETase_TNFα anticancer bacteria can disrupt the tumor microenvironment in the cold LLC tumors and active innate and adaptive anti-cancer immune response in immunocompetent mice. Further, we are investigating additional cold solid mouse tumor models to validate our findings and how this can apply to bacteria-based immunotherapy. Citation Format: Qiuhong He, Lindsay R. Brncick, Boxi Gong, Julia L. Flowers. M1-like macrophage infiltration, CD8+ T cell activation, and increased cancer cell apoptosis in immunologically cold Lewis lung carcinoma treated with tumor-trophic Salmonella Typhimurium expressing anticancer proteins in immunocompetent C57BL/6 mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 184.