M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-02-20 DOI:10.1016/j.tranon.2025.102324

Tetsuya Fukui , Ryota Sumitomo , Toshi Menju , Masashi Kobayashi , Hiroaki Sakai , Hiroshi Date

{"title":"M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma","authors":"Tetsuya Fukui , Ryota Sumitomo , Toshi Menju , Masashi Kobayashi , Hiroaki Sakai , Hiroshi Date","doi":"10.1016/j.tranon.2025.102324","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Malignant pleural mesothelioma (MPM) is an aggressive malignancy with an unfavorable prognosis. Asbestos-activated macrophages may contribute to both oncogenesis and progression of MPM. This study aimed to clarify the biological and clinical significance of M2-like tumor-associated macrophages (TAMs) in MPM.</div></div><div><h3>Methods</h3><div>This retrospective study included 101 MPM patients who were diagnosed and started treatment between 1998 and 2010. The distribution of M2-like TAMs in the intratumoral and peritumoral regions was evaluated by immunohistochemistry using CD163 staining. Tumor proliferation was evaluated by Ki-67 staining.</div></div><div><h3>Results</h3><div>Intratumoral M2-like TAM density was significantly correlated with the pretreatment C-reactive protein level (<em>r</em> = 0.283, <em>P</em> = 0.004) and Ki-67 proliferation index (<em>r</em> = 0.498, <em>P</em> < 0.001). Peritumoral M2-like TAM density was also significantly correlated with the pretreatment C-reactive protein level (<em>r</em> = 0.255, <em>P</em> = 0.010) and Ki-67 proliferation index (<em>r</em> = 0.435, <em>P</em> < 0.001). Additionally, intratumoral M2-like TAM density was associated with histological subtype (<em>P</em> < 0.001), with higher densities observed in sarcomatoid tumors compared to epithelioid tumors. The overall survival rate was significantly worse in the intratumoral and peritumoral M2-like TAM-high groups (<em>P</em> = 0.044 and <em>P</em> = 0.046, respectively), particularly in patients with advanced-stage MPM. Multivariable analysis identified peritumoral M2-like TAM status (hazard ratio = 1.700, 95 % confidence interval: 1.034–2.796, <em>P</em> = 0.037), clinical stage, and histology as significant prognostic factors for overall survival.</div></div><div><h3>Conclusions</h3><div>During MPM progression, M2-like TAMs may induce tumor cell proliferation and aggressiveness, contributing to the poor prognosis in MPM patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102324"},"PeriodicalIF":5.0000,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523325000555","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with an unfavorable prognosis. Asbestos-activated macrophages may contribute to both oncogenesis and progression of MPM. This study aimed to clarify the biological and clinical significance of M2-like tumor-associated macrophages (TAMs) in MPM.

Methods

This retrospective study included 101 MPM patients who were diagnosed and started treatment between 1998 and 2010. The distribution of M2-like TAMs in the intratumoral and peritumoral regions was evaluated by immunohistochemistry using CD163 staining. Tumor proliferation was evaluated by Ki-67 staining.

Results

Intratumoral M2-like TAM density was significantly correlated with the pretreatment C-reactive protein level (r = 0.283, P = 0.004) and Ki-67 proliferation index (r = 0.498, P < 0.001). Peritumoral M2-like TAM density was also significantly correlated with the pretreatment C-reactive protein level (r = 0.255, P = 0.010) and Ki-67 proliferation index (r = 0.435, P < 0.001). Additionally, intratumoral M2-like TAM density was associated with histological subtype (P < 0.001), with higher densities observed in sarcomatoid tumors compared to epithelioid tumors. The overall survival rate was significantly worse in the intratumoral and peritumoral M2-like TAM-high groups (P = 0.044 and P = 0.046, respectively), particularly in patients with advanced-stage MPM. Multivariable analysis identified peritumoral M2-like TAM status (hazard ratio = 1.700, 95 % confidence interval: 1.034–2.796, P = 0.037), clinical stage, and histology as significant prognostic factors for overall survival.

Conclusions

During MPM progression, M2-like TAMs may induce tumor cell proliferation and aggressiveness, contributing to the poor prognosis in MPM patients.

查看原文本刊更多论文

导言恶性胸膜间皮瘤（MPM）是一种侵袭性恶性肿瘤，预后不良。石棉激活的巨噬细胞可能有助于 MPM 的肿瘤发生和发展。本研究旨在阐明 M2 样肿瘤相关巨噬细胞（TAMs）在 MPM 中的生物学和临床意义。通过CD163染色免疫组化评估了M2样肿瘤相关巨噬细胞在瘤内和瘤周区域的分布。结果瘤内 M2 样 TAM 密度与治疗前 C 反应蛋白水平（r = 0.283，P = 0.004）和 Ki-67 增殖指数（r = 0.498，P <0.001）显著相关。瘤周 M2 样 TAM 密度也与治疗前 C 反应蛋白水平（r = 0.255，P = 0.010）和 Ki-67 增殖指数（r = 0.435，P <0.001）显著相关。此外，瘤内 M2 样 TAM 密度与组织学亚型相关（P <0.001），与上皮样肿瘤相比，肉瘤的密度更高。瘤内和瘤周 M2 样 TAM 高组的总生存率明显较低（分别为 P = 0.044 和 P = 0.046），尤其是晚期 MPM 患者。多变量分析发现，瘤周 M2 样 TAM 状态（危险比 = 1.700，95 % 置信区间：1.034-2.796，P = 0.037）、临床分期和组织学是影响总生存期的重要预后因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.