New insights into macrophage polarization and its prognostic role in patients with colorectal cancer liver metastasis

期刊论文
出版模式：

开放获取
发表日期：

2024年4月26日

查看全文

Isha Khanduri,
Harufumi Maki,
Anuj Verma,
Riham Katkhuda,
Gayathri Anandappa,
Renganayaki Pandurengan,
Shanyu Zhang,
Alicia Mejia,
Zhimin Tong,
Luisa M. Solis Soto,
Akshaya Jadhav,
Ignacio I. Wistuba,
David Menter,
Scott Kopetz,
Edwin R. Parra,
Jean-Nicolas Vauthey,
Dipen M. Maru

摘要

Background

As liver metastasis is the most common cause of mortality in patients with colorectal cancer, studying colorectal cancer liver metastasis (CLM) microenvironment is essential for improved understanding of tumor biology and to identify novel therapeutic targets.

Methods

We used a multiplex immunofluorescence platform to study tumor associated macrophage (TAM) polarization and adaptive T cell subtypes in tumor samples from 105 CLM patients (49 without and 56 with preoperative chemotherapy).

Results

CLM exhibited M2 macrophage polarization, and helper T cells were the prevalent adaptive T cell subtype. The density of total, M2 and TGFβ-expressing macrophages, and regulatory T cells was lower in CLM treated with preoperative chemotherapy. CLM with right-sided primary demonstrated enrichment of TGFβ-expressing macrophages, and with left-sided primary had higher densities of helper and cytotoxic T cells. In multivariate analysis, high density of M2 macrophages correlated with longer recurrence-free survival (RFS) in the entire cohort [hazard ratio (HR) 0.425, 95% CI 0.219–0.825, p = 0.011) and in patients without preoperative chemotherapy (HR 0.45, 95% CI 0.221–0.932, p = 0.032). High pSMAD3-expressing macrophages were associated with shorter RFS in CLM after preoperative chemotherapy.

Conclusions

Our results highlight the significance of a multi-marker approach to define the macrophage subtypes and identify M2 macrophages as a predictor of favorable prognosis in CLM.