Presurgical immune checkpoint blockade Checkpoint blockade immunotherapy using antibodies that inhibit the programmed cell death 1 (PD-1) or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) pathways has resulted in unprecedented clinical outcomes for certain cancers such as melanoma. Topalian et al. review advances in neoadjuvant (presurgical) immunotherapy as an important next step for enhancing the response of early-stage tumors to immune checkpoint blockade. They highlight the mechanistic rationale for neoadjuvant immunotherapy and recent neoadjuvant clinical trials based on anti–PD-1 or anti–PD-1 ligand 1 (anti–PD-L1) therapy. Pathological assessment criteria that may provide early on-treatment biomarkers to predict patient response are also discussed. Science , this issue p. eaax0182