Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 72, Issue 5, Pages 1247-1260Publisher
SPRINGER
DOI: 10.1007/s00262-022-03329-8
Keywords
MAIT cells; Fecal microbiota transplantation; Renal cell carcinoma; Kidney cancer; MR1; Cytokine
Categories
Ask authors/readers for more resources
This study assessed the impact of fecal microbiota transplantation (FMT) on innate-like, antimicrobial T lymphocytes in metastatic renal cell carcinoma (mRCC) patients. The results showed that FMT improved the function of mucosa-associated invariant T (MAIT) cells, which could benefit patients in subsequent microbial challenges in the face of cancer-elicited immunosuppression.
Strategies to modify the gut microbiome in cancer patients using fecal microbiota transplantation (FMT) have gained momentum as a therapeutic intervention. However, how FMT impacts innate-like, antimicrobial T lymphocytes is unclear. In this study, we assessed peripheral blood (PB) mucosa-associated invariant T (MAIT) cell frequencies and functions in patients with metastatic renal cell carcinoma (mRCC) before and seven days after they received FMT as part of a clinical trial. We found comparable MAIT cell frequencies in healthy controls and mRCC patients. In contrast, gamma delta T cells exhibited a numerical decline in mRCC, which was partially reversed by FMT. We also found a significant increase in the PB CD4(+) MAIT cell compartment of mRCC patients with or without FMT. Paired sample analyses revealed CD69 upregulation on MAIT cells accompanied by decreased PD-1 levels post-FMT. These changes were unique to MAIT cells as non-MAIT T lymphocytes showed either no trend or a trend in the opposite direction. Importantly, FMT did not render MAIT cells exhausted as also judged by their stable expression of TIM-3, LAG-3, BTLA, CTLA-4, TIGIT and VISTA. These findings were corroborated in functional assays in which MAIT cells were stimulated with MR1 ligands or with a combination of IL-12 and IL-18 to produce inflammatory cytokines and granzyme B. Indeed, when stimulated ex vivo with IL-12 and IL-18, MAIT cells mounted a more rigorous TNF-alpha response post-FMT. In conclusion, FMT improves MAIT cell functions, which should serve patients well in subsequent microbial challenges in the face of cancer-elicited immunosuppression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available