Immunotherapy in gastrointestinal cancers: advances, challenges, and countermeasures

Cancer immunotherapy,largely based on programmed cell death-1(PD-1)/PD-ligand 1(PD-L1)immune checkpoint blockade,has achieved remarkable advancements over the past decade in the treatment of human cancers[1,2],including a subset of gastroin-testinal malignancies[3].Phase 3 randomized studies have demonstrated the efficacy of the PD-1 inhibitor nivolumab as a third-line treatment for chemorefractory advanced gastric cancer(aGC;NCT02267343)and several PD-1 inhibitors(pembrolizumab,nivolumab,tislelizumab,and camrelizumab)as second-line thera-pies for advanced esophageal cancer(NCT02564263/NCT02569242/NCT03430843/NCT03099382);however,the objec-tive response rate(ORR)for this therapy is moderate(approxi-mately 15％).