Abstract
SummaryGrowing 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.
Highlights
The era of cancer immunotherapy is in full swing, and different forms of treatment, such as checkpoint blockade immunotherapy, show uneven effects on restoring T cell immune responses
We observed that Mucosa-associated invariant T (MAIT) cells accounted for a higher proportion of total T cells in colorectal cancer (CRC) compared with non-small cell lung carcinoma (NSCLC) and renal cell carcinoma (RCC) (Figure 1A)
Using a 39-parameter panel, we focused our analysis on profiling tumor-infiltrating MAIT cells from CRC compared with PBMC and healthy adjacent tissue used as references
Summary
The era of cancer immunotherapy is in full swing, and different forms of treatment, such as checkpoint blockade immunotherapy, show uneven effects on restoring T cell immune responses. The TCR-b chains are more diverse, with a bias toward Vb2 and Vb13.3,4,8,9 In 2012, identification of riboflavin precursor derivatives as the microbial ligands for MAIT cells allowed synthesis of MR1 tetramers to identify these cells.[10,11] Most human MAIT cells are CD8+, express the effector/memory phenotype CD45RO+ CD62Llo CCR7À, and are IL-18Rhi 3. They are known to protect against bacterial infection, are reported to be depleted during viral infection, and are implicated in several autoimmune diseases, including diabetes.[12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
