Activating a collaborative innate-adaptive immune response to control metastasis.

Sun, Lijuan, Kees, Tim, Almeida, Ana Santos, Liu, Bodu, He, Xue-Yan, Ng, David, Han, Xiao, Spector, David L, McNeish, Iain A, Gimotty, Phyllis, Adams, Sylvia, Egeblad, Mikala (September 2021) Activating a collaborative innate-adaptive immune response to control metastasis. Cancer Cell. ISSN 1535-6108

URL: https://www.ncbi.nlm.nih.gov/pubmed/34478639
DOI: 10.1016/j.ccell.2021.08.005

Abstract

Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lipid A (MPLA) and interferon (IFN) γ. MPLA + IFNγ injected intratumorally or intraperitoneally reduces primary tumor growth and metastasis in breast cancer mouse models, suppresses metastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophages and T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNγ stimulates type I IFN signaling, reprograms CD206+ TAMs to inducible NO synthase (iNOS)+ macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-2 (IL-12) and tumor necrosis factor alpha (TNFα). MPLA and IFNγ are used individually in clinical practice and together represent a previously unexplored approach for engaging a systemic anti-tumor immune response.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
diseases & disorders > cancer > metastasis
CSHL Authors:
Communities: CSHL labs > Egeblad lab
CSHL labs > Spector lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 1 September 2021
Date Deposited: 07 Sep 2021 13:54
Last Modified: 07 Sep 2021 13:54
URI: https://repository.cshl.edu/id/eprint/40344

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