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

• DOI: 10.7554/elife.70848
• Publication Date: 2022-04-05T00:00:13Z
• Authors: Chie Sugimoto; Yukie Murakami; Eisuke Ishii; Hiroyoshi Fujita; Hiroshi Wakao
• Keywords: 0301 basic medicine; 0303 health sciences; iPSC; anti-metastasis; adoptive transfer; Lung Neoplasms; Mucous Membrane; QH301-705.5; Science; Q; Induced Pluripotent Stem Cells; R; MAIT cells; Adaptive Immunity; Mucosal-Associated Invariant T Cells; Mice; 03 medical and health sciences; Medicine; Animals; NK cell; Biology (General); cytolytic activity; Cancer Biology

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.