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

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, transmi...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307775/
https://www.ncbi.nlm.nih.gov/pubmed/35869130
http://dx.doi.org/10.1038/s41598-022-16766-3
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author 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
author_facet 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
author_sort Park, Ha-Ram
collection PubMed
description 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.
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spelling pubmed-93077752022-07-24 Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis 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 Sci Rep Article 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. Nature Publishing Group UK 2022-07-22 /pmc/articles/PMC9307775/ /pubmed/35869130 http://dx.doi.org/10.1038/s41598-022-16766-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title_full Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title_fullStr Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title_full_unstemmed Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title_short Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
title_sort blockade of cd47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307775/
https://www.ncbi.nlm.nih.gov/pubmed/35869130
http://dx.doi.org/10.1038/s41598-022-16766-3
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