Postdoctoral Associate Scripps Research La Jolla, California, United States
Disclosure(s):
Ayawavi Viviane AGBOGAN, PhD: No financial relationships to disclose
Introduction/Rationale: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that recognize riboflavin-derived metabolites presented by the monomorphic antigen-presenting molecule MR1. MAIT cells are enriched in barrier tissues and tumors, yet their role in cancer remains controversial. Recent evidence suggests that appropriate activation can reprogram MAIT cells toward cytotoxic, Th1/NK-like effector functions. Here, we examined whether MR1-dependent activation of MAIT cells promotes anti-tumor immunity in cutaneous melanoma.
Methods: MAIT cells were activated in vivo using the MR1 agonist 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) combined with the TLR9 agonist CpG. Tumor growth was monitored longitudinally. Immune infiltrates in skin and tumors were analyzed by multiparametric flow cytometry using MR1 tetramers. MR1 dependency and host antigen presentation were assessed using MR1 knockout and conditional MR1 deletion models. Antibody-mediated depletion was used to define the contribution of downstream immune subsets.
Results: MAIT cell activation significantly delayed melanoma growth compared to control-treated mice. Tumor suppression was strictly MR1 dependent, as anti-tumor effects were lost in MR1-deficient hosts. MAIT activation induced robust expansion and accumulation of MAIT cells in skin and tumor tissue and was associated with increased infiltration of NK cells and CD8⁺ T cells. Depletion studies demonstrated that MAIT cells and NK cells were required for tumor control. Conditional deletion of MR1 in host myeloid cells impaired MAIT-mediated anti-tumor immunity, indicating a critical role for MR1-dependent antigen presentation within the tumor microenvironment.
Conclusion: These data demonstrate that MR1-dependent activation licenses MAIT cells as potent anti-tumor effectors that coordinate broader immune responses in melanoma, supporting MR1-MAIT targeting as a potential immunotherapeutic strategy.
