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

T. William Mudd, Chunwan Lu, John D. Klement, Kebin Liu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number104260
JournalCellular Immunology
Volume360
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • CD20
  • Colon carcinoma
  • Immune checkpoint
  • Immune suppression
  • MS4A1
  • PD-L1
  • T cells

ASJC Scopus subject areas

  • Immunology

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