Tumor recognition by MR1T cells

MR1T cells are a recently discovered population of MR1-restricted unconventional T cells. They are heterogeneous, express variable T cell receptors, and respond to antigens present in tumor cells of different tissue origins. To utilize their anti-tumor potential in therapy, it is essential to fully comprehend the range of MR1T recognition of tumors and identify the structure of tumor-related antigens.
My PhD project aimed to characterize the breadth of MR1T reactivity towards different types of cancer cell lines, organoids, and primary tumors. MR1T cells demonstrated different recognition patterns, with some examining a broad cross-reactivity between almost all tested tumors. In contrast, others were only activated in the presence of a small subset of tumor cells.
A significant finding was that some cancer cells had a far superior ability to stimulate the majority of MR1T clones. This led us to investigate the features of highly stimulatory tumors, focusing on the metabolic changes that could lead to generation of MR1T antigens. We discovered critical metabolic pathways significantly altered in highly stimulatory tumors, including the metabolism of arachidonic acid, glutathione, taurine and hypotaurine, and pyrimidines. These findings shed light on the mechanism of MR1T recognition of cells with altered metabolism, which allows for the accumulation of specific metabolites that give rise to MR1T antigens. These studies have implications beyond cancer, as changes in cell metabolism are also observed in other diseases, including infectious and autoimmune diseases.