Abstract IA026: Activating a collaborative innate-adaptive immune response to control metastasis

Abstract

Tumor-associated macrophages (TAMs) promote metastasis and inhibit cytotoxic T cells. Yet, macrophages can be polarized to kill cancer cells. Macrophage polarization could therefore be a strategy for controlling cancer. We have found that monophosphoryl lipid A (MPLA, a derivative of lipopolysaccharide [LPS]) with IFNγ can polarize macrophages isolated from metastatic pleural effusions of breast cancer patients to kill cancer cells in vitro. Injecting tumors with MPLA+IFNγ reduced primary tumor growth, greatly suppressed metastasis, and enhanced the response to chemotherapy in breast and ovarian cancer mouse models. Both macrophages and T cells were critical for the anti-metastatic effects of MPLA+IFNγ. Mechanistically, the combined MPLA+IFNγ treatment stimulated type I interferon signaling, reprogramed TAMs (CD206⁺) to tumoricidal macrophages (iNOS⁺), and activated cytotoxic T cells through macrophage-secreted interleukin 12 (IL-12) and tumor necrosis factor α (TNFα). MPLA and IFNγ are already used individually in clinical practice and together represent a previously unexplored approach to engage a systemic anti-tumor immune response. Citation Format: Mikala Egeblad. Activating a collaborative innate-adaptive immune response to control metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA026.