Background: Gastrointestinal malignancies have both a high incidence rate and a high mortality rate. Immuno-oncological treatment approaches are becoming increasingly established in the treatment of gastrointestinal cancers. Summary: In this review, we give an overview of the types and effects of immunotherapies. We focus on recent studies on immunotherapies with special attention to immune checkpoint inhibition in carcinomas of the esophagus and stomach, the hepato-pancreatico-biliary system, and the colorectum including the anal channel in the metastatic setting, and we show their achievements but also their limitations. In an outlook, we discuss new approaches in immunotherapy like CAR T-cell therapy and oncolytic viruses. Key Messages: Gastrointestinal cancers show overall moderate response rates to immunotherapy. Nevertheless, subgroups such as DNA mismatch repair-deficient or microsatellite-instable tumors particularly benefit from the immune checkpoint blockade. Further studies are ongoing.

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