CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma

Background The immunosuppressive tumor microenvironment is a significant challenge in the treatment of hepatocellular carcinoma (HCC), necessitating the urgent development of strategies to mitigate its effects.Methods The application of bioinformatics methods to predict the expression level of CD24...

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Main Authors: Jun Wang, Jing Xiong, Yu Cheng, Yuan Wu, Shu Jiang, Huimin Zhang, Xiang Xiao, Hanning Li, Yimeng Liu, Jiapeng Li, Jincheng Wang, Zetao Song, Chaojiang Gu, Shaoyong Chen, Yuan Xiang, Xinghua Liao
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/8/e012118.full
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author Jun Wang
Jing Xiong
Yu Cheng
Yuan Wu
Shu Jiang
Huimin Zhang
Xiang Xiao
Hanning Li
Yimeng Liu
Jiapeng Li
Jincheng Wang
Zetao Song
Chaojiang Gu
Shaoyong Chen
Yuan Xiang
Xinghua Liao
author_facet Jun Wang
Jing Xiong
Yu Cheng
Yuan Wu
Shu Jiang
Huimin Zhang
Xiang Xiao
Hanning Li
Yimeng Liu
Jiapeng Li
Jincheng Wang
Zetao Song
Chaojiang Gu
Shaoyong Chen
Yuan Xiang
Xinghua Liao
author_sort Jun Wang
collection DOAJ
description Background The immunosuppressive tumor microenvironment is a significant challenge in the treatment of hepatocellular carcinoma (HCC), necessitating the urgent development of strategies to mitigate its effects.Methods The application of bioinformatics methods to predict the expression level of CD24 in HCC and its relationship with the occurrence and development of HCC. Gene-engineered mice and flow cytometry were used to study the immune cell populations regulated by CD24. Cell metabolism analysis, western blotting, and lactate content measurement were employed to assess the impact of CD24 on lactate secretion by HCC cells. Additionally, cell counting kit 8 and colony formation assays were conducted to evaluate the effect of CD24 on the sensitivity of HCC cells to sorafenib. The integration of RNA sequencing, flow cytometry, cell chemotaxis experiments, and ELISA established a robust framework for understanding CD24-mediated neutrophils immune infiltration.Results In this study, we found that CD24 can recruit neutrophils to infiltrate HCC tissues to form tumor-associated neutrophils (TANs) and polarize TANs to a protumor phenotype by promoting lactate secretion by HCC cells, thus promoting the progression of HCC. In addition, targeting CD24 can enhance the sensitivity of HCC cells to sorafenib by reducing the accumulation of TANs.Conclusions Our results reveal the molecular mechanism by which CD24 promotes HCC progression through recruitment of neutrophils infiltrates, raising new insights into the role of targeting CD24 in driving HCC immunotherapy.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-0b463b073eae475a94182b149d3950a02025-08-22T04:30:13ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2025-012118CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinomaJun Wang0Jing Xiong1Yu Cheng2Yuan Wu3Shu Jiang4Huimin Zhang5Xiang Xiao6Hanning Li7Yimeng Liu8Jiapeng Li9Jincheng Wang10Zetao Song11Chaojiang Gu12Shaoyong Chen13Yuan Xiang14Xinghua Liao151 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China3 Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China5 School of basic medical sciences, Xinxiang Medical University, Xinxiang, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China2 Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China6 Department of Medical Laboratory, Central Hospital of Wuhan, Wuhan, Hubei, China1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, ChinaBackground The immunosuppressive tumor microenvironment is a significant challenge in the treatment of hepatocellular carcinoma (HCC), necessitating the urgent development of strategies to mitigate its effects.Methods The application of bioinformatics methods to predict the expression level of CD24 in HCC and its relationship with the occurrence and development of HCC. Gene-engineered mice and flow cytometry were used to study the immune cell populations regulated by CD24. Cell metabolism analysis, western blotting, and lactate content measurement were employed to assess the impact of CD24 on lactate secretion by HCC cells. Additionally, cell counting kit 8 and colony formation assays were conducted to evaluate the effect of CD24 on the sensitivity of HCC cells to sorafenib. The integration of RNA sequencing, flow cytometry, cell chemotaxis experiments, and ELISA established a robust framework for understanding CD24-mediated neutrophils immune infiltration.Results In this study, we found that CD24 can recruit neutrophils to infiltrate HCC tissues to form tumor-associated neutrophils (TANs) and polarize TANs to a protumor phenotype by promoting lactate secretion by HCC cells, thus promoting the progression of HCC. In addition, targeting CD24 can enhance the sensitivity of HCC cells to sorafenib by reducing the accumulation of TANs.Conclusions Our results reveal the molecular mechanism by which CD24 promotes HCC progression through recruitment of neutrophils infiltrates, raising new insights into the role of targeting CD24 in driving HCC immunotherapy.https://jitc.bmj.com/content/13/8/e012118.full
spellingShingle Jun Wang
Jing Xiong
Yu Cheng
Yuan Wu
Shu Jiang
Huimin Zhang
Xiang Xiao
Hanning Li
Yimeng Liu
Jiapeng Li
Jincheng Wang
Zetao Song
Chaojiang Gu
Shaoyong Chen
Yuan Xiang
Xinghua Liao
CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
Journal for ImmunoTherapy of Cancer
title CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
title_full CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
title_fullStr CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
title_full_unstemmed CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
title_short CD24 recruits tumor-associated neutrophils to promote the progression of hepatocellular carcinoma
title_sort cd24 recruits tumor associated neutrophils to promote the progression of hepatocellular carcinoma
url https://jitc.bmj.com/content/13/8/e012118.full
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