Egeblad, Mikala (2021) Activating a collaborative innate-adaptive immune response to control metastasis. In: AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities, 2021 Jan 11-12, Philadelphia, PA.
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.
| Item Type: | Conference or Workshop Item (Speech) |
|---|---|
| Subjects: | diseases & disorders > cancer 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 |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 2021 |
| Date Deposited: | 28 Sep 2023 19:40 |
| Last Modified: | 27 Nov 2023 16:30 |
| PMCID: | PMC8981964 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41049 |
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