Advances in immunotherapy for gastrointestinal malignancies

Gastrointestinal malignancies remain leading causes of cancer mortality, yet their sensitivity to immunotherapy differs sharply across anatomical sites, histologies, molecular subtypes, and disease stages. Immune checkpoint blockade has established durable clinical benefit in microsatellite instability-high colorectal cancer, advanced gastric and esophageal cancers, hepatocellular carcinoma, and biliary tract cancer, while pancreatic ductal adenocarcinoma and microsatellite-stable colorectal cancer remain largely refractory. Recent phase III trials have moved immunotherapy into perioperative treatment. Concurrently, claudin 18.2-directed chimeric antigen receptor T cells, T-cell receptor-engineered cells, bispecific antibodies, personalized vaccines, and oncolytic viruses are converting previously speculative strategies into clinically testable platforms. This review integrates contemporary trial evidence with mechanisms of immune escape, biomarker development, and combination toxicity. The resulting framework prioritizes evidence maturity across diverse gastrointestinal tumor types worldwide.