A study on the correlation between M2 macrophages and regulatory T cells in the progression of colorectal cancer

Int J Biol Markers. 2022 Dec;37(4):412-420. doi: 10.1177/03936155221132572. Epub 2022 Oct 26.

Abstract

Background: M2 macrophages and regulatory T cells (Tregs) can promote tumors and development by inhibiting the anti-tumor immune response. This study investigated the effect of CD163-positive M2 macrophages and Foxp3-positive Tregs in the progression of colorectal cancer and lymph node metastasis. It also investigated the correlation between M2 macrophages and Tregs.

Methods: Postoperative tissue specimens and clinical data were collected from 197 patients with colorectal cancer who underwent initial surgical treatment in The Second Ward of Colorectal Surgery of the First Affiliated Hospital of Jinzhou Medical University from March 2020 to December 2020. Immunohistochemical methods were used to detect the expression levels of CD163 protein-labeled M2 macrophages and Foxp3 protein-labeled Tregs in colorectal cancer tissues, matched paracancer tissues, and lymph node tissues. The correlation between CD163 and Foxp3 in cancer tissues and lymph node tissues were analyzed, as well as the relationship between clinicopathological characteristics and preoperative tumor markers.

Results: M2 macrophages and Tregs were importantly positively correlated in cancer and lymph node tissues, which significantly increased in cancer and metastatic lymph node tissues. Interestingly, M2 macrophages in non-metastatic lymph nodes also increased significantly in patients with metastatic lymph nodes. In addition, both CD163 and Foxp3 were upregulated with increasing tumor node metastasis stage, depth of infiltration, and lymphatic metastasis; and both were positively correlated with carcinoembryonic antigen.

Conclusion: CD163 may be a good predictor of pre-metastatic status of colorectal cancer lymph nodes. carcinoembryonic antigen affects the distribution of M2 macrophages and Tregs in colorectal cancer. There is a certain correlation between the two types of cells. It is possible that M2 macrophages, together with suppressor Tregs cells, promote an immunosuppressive environment.

Keywords: CD163; Colorectal cancer; Foxp3; M2 macrophages; lymph node metastasis; regulatory T cells.

MeSH terms

  • Carcinoembryonic Antigen / metabolism
  • Colorectal Neoplasms* / pathology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphatic Metastasis / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • T-Lymphocytes, Regulatory* / metabolism
  • T-Lymphocytes, Regulatory* / pathology

Substances

  • Carcinoembryonic Antigen
  • Forkhead Transcription Factors