Mucosal-associated invariant T cells recognize a tumor-derived metabolite in the DNA synthesis pathway - Report - MDSpire

Mucosal-associated invariant T cells recognize a tumor-derived metabolite in the DNA synthesis pathway

  • By

  • Yanqi Xue

  • Yuka Yamada

  • Rikako Suzuki

  • Brenda Luong

  • Shotaro Fujii

  • Keisuke Nakata

  • Masatomo Takahashi

  • Yoshihiro Izumi

  • Chihiro Fukui

  • Ryosuke Takasaki

  • Francois Legoux

  • Shinsuke Inuki

  • Daisuke Motooka

  • Emi Ito

  • Bridget L. Stocker

  • Mattie S. M. Timmer

  • Takashi Shimizu

  • Yasumasa Matsuoka

  • Jun’ichi Mano

  • Koji Tamada

  • Makoto Furutani-Seiki

  • Kei Sakamoto

  • Koh-Hei Sonoda

  • Olivier Lantz

  • Sho Yamasaki

  • Kensuke Shibata

  • June 24, 2026

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Mucosal-associated invariant T cells detect a metabolite from tumors involved in the DNA synthesis pathway

Overview

This study identifies 5-formyl tetrahydrofolate (5-formyl THF) as the first tumor-derived ligand recognized by mucosal-associated invariant T (MAIT) cells in both humans and mice. The activation of MAIT cells by 5-formyl THF is reported to be dependent on the enzyme amino methyltransferase (Amt), which is crucial for its generation in tumor cells.

Background

Cancer remains a leading cause of mortality globally, and the role of T cells in tumor immunity is critical. MAIT cells, a subset of T cells, have been implicated in tumor responses, yet their specific ligands in the context of cancer have not been well characterized. Understanding the interactions between MAIT cells and tumor-derived metabolites is essential for elucidating their biology in the tumor microenvironment.

Data Highlights

No numerical data or trial data provided in the source material.

Key Findings

  • 5-formyl THF is identified as a tumor-derived ligand that activates MAIT cells.
  • The activation of MAIT cells by 5-formyl THF is weaker than that induced by the known agonist 5-OP-RU.
  • Amino methyltransferase (Amt) is essential for the production of 5-formyl THF in tumors.
  • Genetic deletion of Amt in tumors impairs MAIT cell activation.
  • Overexpression of Amt enhances the agonistic activity of MAIT cells.
  • A human MAIT cell clonotype reactive to 5-formyl THF was identified using single-cell TCR sequencing analysis.

Clinical Implications

Further research is needed to explore the functional relevance of the identified ligand 5-formyl THF in vivo.

Conclusion

This study establishes 5-formyl THF as a ligand for MAIT cells, highlighting a novel interaction between tumor metabolism and immune response.

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  5. Gastric Cancer — Genomic Analysis and Molecular Characterization of Somatic Copy Number Variations in Gastric Intramucosal Neoplasias According to Microsatellite Status
  6. SITC Gastrointestinal Cancer Immunotherapy Guideline - Society for Immunotherapy of Cancer (SITC)
  7. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma | FDA
  8. Recognition of vitamin B metabolites by mucosal-associated invariant T cells | Nature Communications

Original Source(s)

Mucosal-associated invariant T cells recognize a tumor-derived metabolite in the DNA synthesis pathway

  • by Yanqi Xue, Yuka Yamada, Rikako Suzuki, Brenda Luong, Shotaro Fujii, Keisuke Nakata, Masatomo Takahashi, Yoshihiro Izumi, Chihiro Fukui, Ryosuke Takasaki, Francois Legoux, Shinsuke Inuki, Daisuke Motooka, Emi Ito, Bridget L. Stocker, Mattie S. M. Timmer, Takashi Shimizu, Yasumasa Matsuoka, Jun’ichi Mano, Koji Tamada, Makoto Furutani-Seiki, Kei Sakamoto, Koh-Hei Sonoda, Olivier Lantz, Sho Yamasaki, Kensuke Shibata

  • June 24, 2026

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