Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer

Cell Reports Medicine
Shamin LiEvan W Newell

Abstract

Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy in human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look for evidence of bacterial antigen recognition in human colon, lung, and kidney carcinomas. Using mass cytometry and single-cell mRNA sequencing, we identify a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 and observe high expression of CD39 on MAIT cells from colorectal cancer (CRC) only, which we show in vitro to be expressed specifically after TCR stimulation. We further reveal that these cells are phenotypically and functionally exhausted. Sequencing data show high bacterial infiltration in CRC tumors and highlight an enriched species, Fusobacteria nucleatum, with capability to activate MAIT cells in a TCR-dependent way. Our results provide evidence of a MAIT cell response to microbial antigens in CRC and could pave the way for manipulating MAIT cells or the microbiome for cancer therapy.

Associated Datasets

Citations

Mar 13, 2021·Frontiers in Immunology·Tejeshwar JainVikas Dudeja
Apr 4, 2021·Cancers·Dasha T CogswellRichard P Tobin
Apr 4, 2021·Cancers·Chloe O'NeillAndrew E Hogan
Apr 23, 2021·Cancer Immunology, Immunotherapy : CII·William RodinMarianne Quiding Järbrink
Jul 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Shamin LiEvan W Newell

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Datasets Mentioned

BETA
GSE15184

Methods Mentioned

BETA
flow cytometry
scRNA-seq
flow
scRNAseq
Assay
RNA-Seq
PCA
FACS
Single Cell Capture

Software Mentioned

uwot
R package
BioTrust
Fluidigm
BWA aligner
R scripts
Kraken
stats
Seurat
R

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