MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment

Cell Immunol. 2021 Feb;360:104260. doi: 10.1016/j.cellimm.2020.104260. Epub 2020 Dec 14.

Abstract

The majority of human colorectal cancer remains resistant to immune checkpoint inhibitor (ICI) immunotherapy, but the underlying mechanism is incompletely understood. We report here that MS4A1, the gene encoding B cell surface marker CD20, is significantly downregulated in human colorectal carcinoma. Furthermore, MS4A1 expression level in colorectal carcinoma is positively correlated with patient survival. Analysis of scRNA-Seq dataset from public database revealed that MS4A1 is also expressed in subsets of T cells. A CD8+CD20+ subset of T cells exists in the neighboring non-neoplastic colon but disappears in tumor in human colorectal carcinoma. Furthermore, analysis of a published nivolumab treatment dataset indicated that nivolumab-bound T cells from human patients during anti-PD-1 immunotherapy exhibit significantly higher MS4A1 expression. Our findings indicate that CD8+CD20+ T subset functions in host cancer immunosurveillance and tumor microenvironment suppresses this T subset through a PD-L1-dependent mechanism.

Keywords: CD20; Colon carcinoma; Immune checkpoint; Immune suppression; MS4A1; PD-L1; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD20 / genetics
  • Antigens, CD20 / metabolism
  • B7-H1 Antigen / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Databases, Factual
  • Female
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antigens, CD20
  • B7-H1 Antigen
  • CD274 protein, human
  • Glycoproteins
  • MS4A1 protein, human
  • Programmed Cell Death 1 Receptor