Bibliographic Details
| Title: |
Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis. |
| Authors: |
Kamber, Roarke A., Nishiga, Yoko, Morton, Bhek, Banuelos, Allison M., Barkal, Amira A., Vences-Catalán, Felipe, Gu, Mingxin, Fernandez, Daniel, Seoane, Jose A., Yao, David, Liu, Katherine, Lin, Sijie, Spees, Kaitlyn, Curtis, Christina, Jerby-Arnon, Livnat, Weissman, Irving L., Sage, Julien, Bassik, Michael C. |
| Source: |
Nature; 9/23/2021, Vol. 597 Issue 7877, p549-554, 6p |
| Abstract: |
Monoclonal antibody therapies targeting tumour antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1–7. However, cancer cells evade phagocytosis using mechanisms that are incompletely understood. Here we develop a platform for unbiased identification of factors that impede antibody-dependent cellular phagocytosis (ADCP) using complementary genome-wide CRISPR knockout and overexpression screens in both cancer cells and macrophages. In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly characterized enzyme adipocyte plasma membrane-associated protein (APMAP). We find that loss of APMAP synergizes with tumour antigen-targeting monoclonal antibodies and/or CD47-blocking monoclonal antibodies to drive markedly increased phagocytosis across a wide range of cancer cell types, including those that are otherwise resistant to ADCP. Additionally, we show that APMAP loss synergizes with several different tumour-targeting monoclonal antibodies to inhibit tumour growth in mice. Using genome-wide counterscreens in macrophages, we find that the G-protein-coupled receptor GPR84 mediates enhanced phagocytosis of APMAP-deficient cancer cells. This work reveals a cancer-intrinsic regulator of susceptibility to antibody-driven phagocytosis and, more broadly, expands our knowledge of the mechanisms governing cancer resistance to macrophage phagocytosis.CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
