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

Our plain-English summary of M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma, by T. Fukui, R. Sumitomo, T. Menju, et al (Translational Oncology, 2025).

The study

• Authors: T. Fukui, R. Sumitomo, T. Menju, M. Kobayashi, H. Sakai, H. Date
• Journal: Translational Oncology
• Published: 2025;54:102324
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2025. Published by Elsevier Inc.

In plain English

This retrospective study examined tumor tissue from 101 patients with malignant pleural mesothelioma treated at two hospitals in Japan between 1998 and 2010. The authors stained the tissue to count immune cells called M2-like tumor-associated macrophages inside the tumor and in the tissue next to it. They also scored the percentage of tumor cells staining for Ki-67, a marker of cell proliferation. Higher macrophage density in both areas was correlated with a blood marker of inflammation (C-reactive protein) and with a higher Ki-67 index. Density inside the tumor was highest in sarcomatoid tumors and lowest in epithelioid tumors. Five-year survival was lower in patients with high macrophage counts, mainly in advanced-stage disease. After adjustment for other factors, a high count next to the tumor was linked to a higher risk of death (hazard ratio 1.700, 95% confidence interval 1.034 to 2.796), as were stage and tumor type. Forty-three patients had reported asbestos exposure, and this was not significantly linked to macrophage density or survival. The authors concluded that these macrophages might promote tumor progression. They noted that the study was retrospective and relatively small.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective study of tumor tissue (immunohistochemistry) and patient survival
• Who was studied: 101 patients with malignant pleural mesothelioma (57 epithelioid, 19 biphasic, 25 sarcomatoid) treated at Kyoto University Hospital or Hyogo Prefectural Amagasaki General Medical Center, Japan, January 1998 to December 2010; 5 of 106 patients were excluded for missing C-reactive protein data
• Exposure: Density of M2-like tumor-associated macrophages (cells stained for CD163) inside the tumor and in the tissue next to the tumor. Asbestos exposure history was recorded as a patient characteristic (43 yes, 58 no); no fiber types are given.
• Main results:
  • Macrophage density inside the tumor was weakly correlated with pretreatment C-reactive protein level (r = 0.283, P = 0.004)
  • Macrophage density inside the tumor was correlated with the Ki-67 proliferation index, the percentage of tumor cells staining for Ki-67 (r = 0.498, P less than 0.001)
  • Macrophage density next to the tumor was weakly correlated with C-reactive protein (r = 0.255, P = 0.010) and correlated with the Ki-67 index (r = 0.435, P less than 0.001)
  • Macrophage density inside the tumor was associated with histology (P less than 0.001). Mean densities were 422.3 cells/mm2 in epithelioid, 712.5 in biphasic and 957.6 in sarcomatoid tumors.
  • Five-year overall survival was 13.3% in the high-density group inside the tumor versus 23.2% in the low-density group (P = 0.044). For the tissue next to the tumor it was 13.2% versus 24.1% (P = 0.046).
  • Among advanced-stage patients, five-year survival in the high versus low group next to the tumor was 3.5% versus 24.4% (P = 0.016); inside the tumor it was 7.8% versus 18.4% (P = 0.017). There was no significant difference among early-stage patients.
  • In multivariable analysis, high (versus low) macrophage status next to the tumor was associated with a higher hazard of death from any cause (hazard ratio 1.700, 95% CI 1.034 to 2.796, P = 0.037). Clinical stage III or IV (HR 2.028) and non-epithelioid histology (HR 1.690) were also significant. High status inside the tumor was not significant in this analysis.
  • A history of asbestos exposure (43 patients) was not significantly associated with overall survival in univariable analysis (HR 0.745, 95% CI 0.466 to 1.192, P = 0.219)
  • Macrophage density inside the tumor did not differ significantly by asbestos exposure history (mean 633.3 cells/mm2 in the 43 exposed patients, P = 0.690)
• The authors' conclusion: The authors concluded that M2-like tumor-associated macrophages might promote tumor progression in malignant pleural mesothelioma and may be a potential therapeutic target, and that further studies are needed.
• Limitations the authors state:
  • The study was retrospective with a relatively small sample size
  • The long study period may have involved changes in treatment strategies

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Pleural Mesothelioma, Prognosis, Oncogenesis, Immunohistochemistry, Ki-67, Histological Subtype, Sarcomatoid.

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