SMPD3 and neoplasm: Modulation of nSMase2 can enhance the antitumor response to anti-PD-1 therapy161, but tumor-infiltrating Tregs can reduce the expression of endothelial nSMase2, preventing lymphocyte migration;162 moreover, enriched S1P and LPA in the tumor microenvironment can reprogram the antitumor activity of infiltrated lymphocytes29,163.