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Pharmacological enhancement of MR1 protein expression enhances tumor cell killing by MR1T cells (De Libero Lab)
The De Libero Lab, with Daniel Constantin as the first author, has published an important new study titled "MR1 Gene and Protein Expression Are Enhanced by Inhibition of the Extracellular Signal-Regulated Kinase ERK" in CANCER IMMUNOLOGY RESEARCH.
This research highlights the potential of the MHC class I-related molecule MR1 as a target for cancer immunotherapy. MR1 is highly conserved across mammals and presents bacterial and endogenous antigens in tumor cells. These unique features make MR1 an ideal candidate for tumor-specific T cell therapies.
The team identified ERK1/2 as key negative regulators of MR1 gene and protein expression. Their study demonstrated that inhibiting ERK1/2 in tumor cells, or treatment of BRAF-mutant tumor cells with drugs specific for mutated BRAF, increases MR1 protein levels, thereby enhancing recognition and killing by MR1-restricted T cells. These effects were observed in cancer cell lines from various tissues, including those resistant to BRAF inhibitors, and in primary cancer cells. In contrast, healthy cells showed minimal or no recognition after ERK1/2 inhibition.
The findings suggest a promising pharmacological approach to boost MR1 protein expression in tumor cells, potentially offering a new strategy for activating MR1-restricted T cells in cancer treatment.
The DBM congratulates the De Libero Lab and their collaborators for this outstanding achievement and their contribution to advancing cancer immunotherapy.