Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation

ABSTRACT Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecule...

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Main Authors: Tao Huang, Longqian Wei, Huafu Zhou, Jun Liu
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.70604
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author Tao Huang
Longqian Wei
Huafu Zhou
Jun Liu
author_facet Tao Huang
Longqian Wei
Huafu Zhou
Jun Liu
author_sort Tao Huang
collection DOAJ
description ABSTRACT Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecules and therapeutic strategies related to tumor immunity in ESCC. Methods In this study, we integrated high‐throughput sequencing data, gene chip data, single‐cell sequencing data, and various bioinformatics analysis methods along with experimental approaches to identify key genes involved in immune infiltration in ESCC and investigate their relationship with immune cell development, as well as the potential of these key genes in immunotherapy. Results We discovered and validated a positive correlation between macrophage infiltration and ITGB2 expression in ESCC. ITGB2 is overexpressed in ESCC and has potential as a prognostic biomarker for the disease. We present for the first time the finding that the expression of ITGB2 in infiltrating macrophages increases as these macrophages polarize toward a tumor‐promoting phenotype in ESCC. Moreover, during the progression of ESCC, ITGB2 expression in infiltrating macrophages is upregulated. The higher the expression of ITGB2, the more feasible it is to target macrophages. Additionally, we found that evaluating immune therapy responses in ESCC patients through ITGB2 expression is a viable approach. Furthermore, we identified three miRNAs associated with abnormal ITGB2 expression, providing insights into the upstream molecular interactions of ITGB2. Conclusions Macrophage infiltration in ESCC is closely associated with ITGB2, which holds significant potential for immunotherapy applications in ESCC. Based on our findings and prior studies, we propose a novel hypothesis: inducing M1 macrophages in vitro, knocking out ITGB2, and then reinfusing these ITGB2‐knockout M1 macrophages into ESCC patients may represent a promising new immunotherapy strategy, providing a new avenue for ESCC immunotherapy.
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spelling doaj-art-a55801a40966447f8df097d30e64e2292025-01-24T08:46:07ZengWileyCancer Medicine2045-76342025-01-01142n/an/a10.1002/cam4.70604Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel CorrelationTao Huang0Longqian Wei1Huafu Zhou2Jun Liu3Department of Cardiothoracic Surgery The First Affiliated Hospital of Guangxi Medical University Nanning People's Republic of ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangxi Medical University Nanning People's Republic of ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangxi Medical University Nanning People's Republic of ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangxi Medical University Nanning People's Republic of ChinaABSTRACT Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecules and therapeutic strategies related to tumor immunity in ESCC. Methods In this study, we integrated high‐throughput sequencing data, gene chip data, single‐cell sequencing data, and various bioinformatics analysis methods along with experimental approaches to identify key genes involved in immune infiltration in ESCC and investigate their relationship with immune cell development, as well as the potential of these key genes in immunotherapy. Results We discovered and validated a positive correlation between macrophage infiltration and ITGB2 expression in ESCC. ITGB2 is overexpressed in ESCC and has potential as a prognostic biomarker for the disease. We present for the first time the finding that the expression of ITGB2 in infiltrating macrophages increases as these macrophages polarize toward a tumor‐promoting phenotype in ESCC. Moreover, during the progression of ESCC, ITGB2 expression in infiltrating macrophages is upregulated. The higher the expression of ITGB2, the more feasible it is to target macrophages. Additionally, we found that evaluating immune therapy responses in ESCC patients through ITGB2 expression is a viable approach. Furthermore, we identified three miRNAs associated with abnormal ITGB2 expression, providing insights into the upstream molecular interactions of ITGB2. Conclusions Macrophage infiltration in ESCC is closely associated with ITGB2, which holds significant potential for immunotherapy applications in ESCC. Based on our findings and prior studies, we propose a novel hypothesis: inducing M1 macrophages in vitro, knocking out ITGB2, and then reinfusing these ITGB2‐knockout M1 macrophages into ESCC patients may represent a promising new immunotherapy strategy, providing a new avenue for ESCC immunotherapy.https://doi.org/10.1002/cam4.70604esophageal squamous cell carcinomaimmunotherapyITGB2macrophages
spellingShingle Tao Huang
Longqian Wei
Huafu Zhou
Jun Liu
Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
Cancer Medicine
esophageal squamous cell carcinoma
immunotherapy
ITGB2
macrophages
title Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
title_full Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
title_fullStr Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
title_full_unstemmed Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
title_short Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
title_sort macrophage infiltration and itgb2 expression in escc a novel correlation
topic esophageal squamous cell carcinoma
immunotherapy
ITGB2
macrophages
url https://doi.org/10.1002/cam4.70604
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AT longqianwei macrophageinfiltrationanditgb2expressioninesccanovelcorrelation
AT huafuzhou macrophageinfiltrationanditgb2expressioninesccanovelcorrelation
AT junliu macrophageinfiltrationanditgb2expressioninesccanovelcorrelation