The immunosuppressive actions of regulatory T (Treg) cells have limited the success of cancer immunotherapies. Grinberg-Bleyer et al. show that ablation of the canonical nuclear factor κB (NF-κB) subunit c-rel specifically impairs the generation and maintenance of activated Treg cells and reduces growth of transplanted melanoma cells in mice. Daily injections of the FDA-approved drug pentoxyfylline (PTXF; which inhibits c-rel) similarly reduced the rate of tumour growth in a mouse melanoma transplantation model by altering Treg cell identity and function. Furthermore, combining PTXF with anti-PD1 immunotherapy had an additive effect in treating established melanoma in mice.
References
Grinberg-Bleyer, Y. et al. NF-κB c-rel is crucial for the regulatory T cell immune checkpoint in cancer. Cell 170, 1096–1108 (2017)10.1016/j.cell.2017.08.004.
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Crunkhorn, S. Targeting regulatory T cells. Nat Rev Drug Discov 16, 754 (2017). https://doi.org/10.1038/nrd.2017.206
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DOI: https://doi.org/10.1038/nrd.2017.206