Microbial Metabolites Potentiate MAIT Cell Anti-Tumor Immunity Against Solid Tumors
Year: 2026
Type: preprint
Abstract: Mucosal-associated invariant T (MAIT) cells sense riboflavin metabolites through the monomorphic antigen-presenting molecule MR1, providing a unique opportunity to therapeutically mobilize a broadly shared T cell population without genetic engineering. Here, we show that the highly potent microbial metabolites, 5-OP-RU and 5-OE-RU, can be exploited as pharmacologic precision immune activators to drive human MAIT cell responses against solid tumors. Ligand stimulation in human co-culture systems elicited robust MAIT cell cytotoxicity, inflammatory cytokine secretion, and transcriptional states transformation. In vivo administration of riboflavin ligands 5-OP-RU significantly suppressed tumor growth in xenograft liver cancer models. Metabolite-driven MAIT activation also reprogrammed the local immune landscape, enhancing effector function and overcoming features of the immunosuppressive niche by markedly eliminating tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME). These findings reveal that microbial riboflavin metabolites can power and redirect MAIT cells to solid tumors, establishing MR1–metabolite signaling as a tractable therapeutic axis for liver cancer and other solid malignancies.
Source: eLife
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G3595327501, G3785197112, Combating Ovarian Cancer with Stem Cell-Engineered Off-The-Shelf CAR-NKT Cell Therapy, G4705603570, HSC-Engineered Off-The-Shelf CAR-iNKT Cell Therapy for Multiple Myeloma, Preclinical Development of An HSC-Engineered Off-The-Shelf iNKT Cell Therapy for Cancer, G8023444137
OpenAlex ID: W7214053464