Abstract

Checkpoint inhibitors are being added to standard-of-care chemotherapy in multi-
ple clinical trials. Success has been reported in non–small and small cell lung carci- nomas and urothelial, head and neck, gastric, and esophageal cancers, and promising results are already available in triple-negative breast and pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor cell death, antiangiogenesis, selective depletion of myeloid immunosup- pressive cells, and lymphopenia, which reduces regulatory T cells and makes room for proliferation of effector T cells. However, chemotherapy regimens have not been optimized for such combinations, perhaps explaining some recent clinical trial disappointments. Approaches to make the most of chemo- immunotherapy include neoadjuvant and a…