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

## TL;DR

This study shows that M2-like tumor-associated macrophages are linked to worse outcomes in pleural mesothelioma patients.

## Contribution

The study identifies M2-like TAMs as a novel prognostic factor in malignant pleural mesothelioma.

## Key findings

- High M2-like TAM density correlates with elevated C-reactive protein and Ki-67 index in MPM.
- M2-like TAMs are more abundant in sarcomatoid than epithelioid MPM subtypes.
- High M2-like TAM density is associated with worse overall survival in MPM patients.

## Abstract

•Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis.•The significance of M2-like tumor-associated macrophages (TAMs) was assessed in MPMs.•High M2-like TAM density linked to higher C-reactive protein and Ki-67 index.•In sarcomatoid tumors, M2-like TAMs were more abundant than in epithelioid tumors.•High M2-like TAM density was associated with worse overall survival in MPM patients.

Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis.

The significance of M2-like tumor-associated macrophages (TAMs) was assessed in MPMs.

High M2-like TAM density linked to higher C-reactive protein and Ki-67 index.

In sarcomatoid tumors, M2-like TAMs were more abundant than in epithelioid tumors.

High M2-like TAM density was associated with worse overall survival in MPM patients.

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.

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.

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.

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