Faculty, Staff and Student Publications
Publication Date
4-26-2024
Journal
BJC Reports
Abstract
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.
DOI
10.1038/s44276-024-00056-8
PMID
39516662
PMCID
PMC11523988
PubMedCentral® Posted Date
4-26-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
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