Tumor-associated macrophage infiltration and prognosis in colorectal cancer: systematic review and meta-analysis

Int J Colorectal Dis. 2020 Jul;35(7):1203-1210. doi: 10.1007/s00384-020-03593-z. Epub 2020 Apr 17.

Abstract

Background: Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined.

Objective: This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC.

Methods: Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status.

Results: A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68+ TAM subset correlated with better 5-year OS, while neither CD68+NOS2+ M1 subset nor CD163+ M2 subset was correlated with 5-year OS. Increased CD68+ TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS.

Conclusions: High infiltration of CD68+ TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68+ TAM infiltration may be promising in CRC treatment.

Keywords: Colorectal cancer; Meta-analysis; Overall survival; Prognosis; Tumor-associated macrophage.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antigens, Differentiation, Myelomonocytic
  • Colonic Neoplasms*
  • Humans
  • Macrophages
  • Prognosis
  • Tumor Microenvironment
  • Tumor-Associated Macrophages*

Substances

  • Antigens, Differentiation, Myelomonocytic