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 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.”
Read more in Nature .
Nature
Experimental study
Cells
B-cell-specific checkpoint molecules that regulate anti-tumour immunity
21-Jun-2023
V.K.K. has an ownership interest in and is a member of the scientific advisory board for Tizona Therapeutics, Bicara Therapeutics, Compass Therapeutics, Larkspur Biosciences and Trishula Therapeutics. L.B., S.X. and V.K.K. are named as inventors on a provisional patent that has been filed including work from this study. L.A. performed consultancy work for Roche, Merck, Bristol-Myers Squibb and Orega Biotech, and was a recipient of a research grant from Sanofi. A.R. and V.K.K. are co-founders of and have an ownership interest in Celsius Therapeutics. A.R. is also a co-founder and equity holder in Immunitas Therapeutics and was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Asimov and Neogene Therapeutics until 31 July 2020. A.R. and O.R.-R. are listed as co-inventors on patent applications filed by the Broad Institute to inventions relating to single-cell genomics. The interests of V.K.K. were reviewed and managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict-of-interest policies. The interests of A.R. were reviewed and managed by the Broad Institute and HHMI in accordance with their conflict-of-interest policies. Since 1 August 2020, A.R. has been an employee of Genentech, a member of the Roche group. O.R.-R. is currently an employee of Genentech. The other authors declare no competing interests.