We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis.
- Authors
Park, Ha-Ram; Kim, Seong-Eun; Keam, Bhumsuk; Chung, Hyewon; Seok, Seung Hyeok; Kim, Soyeon; Kim, Miso; Kim, Tae Min; Doh, Junsang; Kim, Dong-Wan; Heo, Dae Seog
- 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.
- Subjects
VASCULAR endothelial growth factor receptors; RENAL cell carcinoma; CD47 antigen; VASCULAR endothelial growth factor antagonists; MACROPHAGES; IMMUNE checkpoint proteins; PHAGOCYTOSIS; PERITONEAL macrophages
- Publication
Scientific Reports, 2022, Vol 12, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-022-16766-3