Longevity & AgingBlocking CD38 Revives Exhausted T Cells and Breaks Immunotherapy Resistance
Researchers at Massachusetts General Hospital found that CD38, an enzyme that degrades NAD+, is highly expressed in exhausted CD8+ T cells in melanoma tumors and strongly predicts resistance to immune checkpoint blockade (ICB). Using patient-derived 3D tumor models called organotypic tumor spheroids, they demonstrated that blocking CD38—either pharmacologically or genetically—restored cellular NAD+ levels, improved mitochondrial function, and boosted T cell effector activity. Combining CD38 blockade with PD-1 inhibition successfully reversed ICB resistance in these human tumor explants, suggesting a promising new therapeutic strategy for melanoma patients who fail standard immunotherapy.
