Immune Cell Marker and Regulator of Anti-Tumor Immunity Uncovered
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B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumor immunity remains unknown. Researchers at Brigham and Women’s Hospital with expertise in immunology collaborated with experts in dermatology from Massachusetts General Hospital (MGH) to further understand the role of B cells and identify a subset of cells that may play a critical role. In collaboration with the Broad Institute, they used a technique called single-cell profiling, which allows them to look at all the genes in the cell to study these B cells in mouse and human cancers.
They found a cell surface receptor called TIM-1 expressed on these B cells during melanoma growth. They also characterized multiple accompanying cell surface proteins that were involved in the B cell’s immune function. Interestingly, they found that deleting a molecule TIM-1, but not any of the other accompanying proteins, dramatically decreased tumor growth. The researchers concluded that TIM-1 controls B cell activation and immune response that combats cancer, including activating another type of the killer tumor-specific T cells for inhibiting tumor growth.
“The collaboration across institutions was extremely fruitful as we combined our immunology expertise at the Brigham with work at David Fisher’s MGH laboratory, where seminal discoveries in skin malignancies have been made,” said lead author Lloyd Bod, PhD, of the Department of Neurology at the Brigham, who conducted this work while completing his postdoctoral fellowship at the Brigham. Bod is now an Assistant Professor and an independent investigator at the Mass General Cancer Center. “The collaboration allowed us to test and demonstrate the therapeutic potential of targeting TIM-1 in melanoma models.”
Reference: Bod L, Kye YC, Shi J, et al. B-cell-specific checkpoint molecules that regulate anti-tumour immunity. Nature. Published online June 21, 2023:1-9. doi: 10.1038/s41586-023-06231-0
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