#ScienceSaturday What if #cancer starts weakening T cells before they even reach the tumor? A new study published in @Nature suggests that an important part of cancer’s immune suppression may happen outside the #tumor itself, in nearby lymph nodes where cancer-fighting T cells are activated and prepared to respond. 🔬 Researchers studied tumor-draining #lymph nodes from patients with melanoma and identified a population of immune cells, mainly macrophages, producing high levels of an enzyme called PLA2G2D. These cells were found close to activated CD8+ T cells and were associated with poorer outcomes. In laboratory and mouse studies, PLA2G2D acted like an immune brake, limiting the early expansion of tumor-specific T cells. When researchers blocked it, more cancer-fighting T cells expanded in the lymph nodes, entered the bloodstream and ultimately reached the tumor. Even more interesting, blocking PLA2G2D alongside PD-1 checkpoint inhibition produced additive or synergistic antitumor effects in preclinical models, suggesting the two pathways may suppress #Tcells in different ways. 💡 Why does this matter? We often focus on overcoming immune suppression inside the tumor. This study suggests there may also be important immune “checkpoints” in the lymph nodes where antitumor responses begin. There is still more work to do before this approach can be tested as a treatment in patients, but understanding these early barriers could reveal new ways to help more tumor-specific T cells make it into the fight. @AvanKrimpen_ @R_Stadhouders @bart_lambrecht @ErasmusMC @tmu2010 @UTokyo_News_en @NatureComms @NatureMedicine Read the study: nature.com/articles/s41586-0…