Reprogramming and redifferentiation of mucosal-associated invariant T cells reveal tumor inhibitory activity

Elife. 2022 Apr 5:11:e70848. doi: 10.7554/eLife.70848.

Abstract

Mucosal-associated invariant T (MAIT) cells belong to a family of innate-like T cells that bridge innate and adaptive immunities. Although MAIT cells have been implicated in tumor immunity, it currently remains unclear whether they function as tumor-promoting or inhibitory cells. Therefore, we herein used induced pluripotent stem cell (iPSC) technology to investigate this issue. Murine MAIT cells were reprogrammed into iPSCs and redifferentiated towards MAIT-like cells (m-reMAIT cells). m-reMAIT cells were activated by an agonist in the presence and absence of antigen-presenting cells and MR1-tetramer, a reagent to detect MAIT cells. This activation accompanied protein tyrosine phosphorylation and the production of T helper (Th)1, Th2, and Th17 cytokines and inflammatory chemokines. Upon adoptive transfer, m-reMAIT cells migrated to different organs with maturation in mice. Furthermore, m-reMAIT cells inhibited tumor growth in the lung metastasis model and prolonged mouse survival upon tumor inoculation through the NK cell-mediated reinforcement of cytolytic activity. Collectively, the present results demonstrated the utility and role of m-reMAIT cells in tumor immunity and provide insights into the function of MAIT cells in immunity.

Keywords: MAIT cells; NK cell; adoptive transfer; anti-metastasis; cancer biology; cytolytic activity; iPSC; mouse; regenerative medicine; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Induced Pluripotent Stem Cells* / metabolism
  • Lung Neoplasms* / metabolism
  • Mice
  • Mucosal-Associated Invariant T Cells*
  • Mucous Membrane

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.