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Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis

Cited 2 time in Web of Science Cited 1 time in Scopus
Authors

Park, Ha-Ram; Kim, Seong-Eun; Keam, Bhumsuk; Chung, Hyewon; Seok, Seung Hyeok; Kim, Soyeon; Kim, Miso; Kim, Tae Min; Doh, JunsangKim, Dong-Wan; Heo, Dae Seog

Issue Date
2022-07
Publisher
Nature Publishing Group
Citation
Scientific Reports, Vol.12 No.1, p. 12546
Abstract
Immune checkpoint inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are mainstream treatments for renal cell carcinoma (RCC). Both T cells and macrophages infiltrate the tumor microenvironment of RCC. CD47, an immune checkpoint of macrophages, transmits the "don't eat me" signal to macrophages. We propose a novel therapeutic strategy that activates the antitumor effect of macrophages. We found that CD47 was expressed in patients with RCC, and high CD47 expression was indicative of worse overall survival in datasets from The Cancer Genome Atlas. We observed that CD47-blocking antibodies enhanced the antitumor effect of macrophages against human RCC cell lines. Trogocytosis, rather than phagocytosis, occurred and was promoted by increased cell-to-cell contact between macrophages and RCC cells. Trogocytosis induced by CD47 blockade occurred in the presence of CD11b integrin signaling in macrophages and was augmented when RCC cells were exposed to VEGFR TKIs, except for sunitinib. In conclusion, this study presents evidence that anti-CD47 blocking antibodies improve the antitumor effect of macrophages in RCC. In combination with VEGFR TKIs, CD47 blockade is a potential therapeutic strategy for patients with RCC.
ISSN
2045-2322
URI
https://hdl.handle.net/10371/185347
DOI
https://doi.org/10.1038/s41598-022-16766-3
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