PREreviews of “Macrophages redeploy functional cancer cell surface proteins following phagocytosis”

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Macrophages redeploy functional cancer cell surface proteins following phagocytosis

by Regan F. Volk, Sara W. Casebeer, Andrew C. Condon, Bahar Zirak, Nayelis Manon, Iryna Irkliyenko, Huajun Liao, Shao Tao, Tommaso Pollini, Vijay Ramani, Ajay V. Maker, Trevor Fidler, Hani Goodarzi, and Balyn W. Zaro

Posted: September 25, 2024
Server: bioRxiv
DOI: 10.1101/2024.09.23.613776

Abstract

Macrophage-mediated phagocytosis is a vital innate immune process altered in cancer. We show here that tumor-associated macrophages (TAMs) redeploy intact cell surface proteins from cancer cells to their own cell surface. We initially observed the canonical epithelial cancer surface marker EpCAM on the surface of TAMs in primary human solid tumors but not paired peripheral blood macrophages. In a murine model of metastatic breast cancer, we also observed EpCAM on the surface of primary TAMs that have phagocytosed breast cancer cells. In a model of a myeloproliferative neoplasm, we again found engulfed cell-derived surface proteins on the surface of macrophages following phagocytosis. A co-culture system and proteomics assay that tags proteins based on their cell-of-origin revealed hundreds of cell surface proteins synthesized in cancer cells are present and fully intact on the surface of macrophages following phagocytosis. Using a biotin transfer assay, we determined that these proteins were on the surface of the cancer cell prior to redeployment by the macrophage following phagocytosis. Furthermore, macrophages that redeploy a neutral amino acid transporter correspondingly show increased transport of an unnatural amino acid substrate. Widespread acquisition of proteins from engulfed cells may contribute to two critical TAM phenotypes: the inability to phagocytose and reprogrammed metabolism.

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PREreview by Yanyang Chen et al. of the ASAPbio Immunology Crowd

Authored by Yanyang Chen, Teena Bajaj, Marina Schernthanner, Peren Coskun, Alex To, Gliday Yuka, and Julia Hansen of the ASAPbio Immunology Crowd
Brief summary of the study - a sentence summarizing the study and general comments that apply across the full paper
- Here, the authors demonstrate how tumor-associated macrophages (TAMs) are able to phagocytose cancer cells and re-express cancer cell-derived proteins on their cellular surface. This…
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PREreviews of Macrophages redeploy functional cancer cell surface proteins following phagocytosis

1 PREreview