01509nam a2200217   4500001000800000005001700008007000300025008004100028040000800069041000800077100003400085245005200119300002500171520091100196650001101107650001501118650001801133650001401151700002301165773010301188ESSALUD20260805102227.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aHotchkiss, Richard S. eAutor  aStemness as the engine of checkpoint durability  apáginas: 2374-2377  aCheckpoint inhibitors have transformed cancer therapy, with 250,000 to 400,000 patients treated annually in the United States. By blocking programmed cell death protein 1 (PD-1) or its ligand (PD-L1), checkpoint inhibitors suppress inhibitory signals that restrain T-cell activation, thereby restoring antitumor immunity. Despite early and sometimes dramatic responses, clinical benefits often wane. Retrospective analyses of checkpoint-inhibitor rechallenge show lower response rates and diminished durability as compared with initial treatment. These observations lead to the question: can prolonged or intensified PD-1 or PD-L1 blockade paradoxically compromise the long-term immune fitness required for sustained tumor control? A recent study by Hor et al. suggests that it does and provides a mechanistic framework that may reshape how checkpoint inhibitors are deployed and their durability extended.  aCANCER  aGENÉTICA  aHEMATOLOGÍA  aINMUNIDAD  aDiPersio, John F. 0 022717dMassachusetts NEJM GroupoNEJM007tThe New England Journal of Medicine wESSALUDx0028-4793