An overview of current immunotherapy approaches for treating gastrointestinal cancers

<h2>Abstract</h2> Gastrointestinal (GI) cancers, account for a substantial proportion of global cancer cases and deaths, and present significant therapeutic challenges. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed the treatment landscape, and offered improved outcomes for patients presenting with various gastrointestinal malignancies. For esophageal cancer, trials like CheckMate 577, KEYNOTE 590, 811, and MATTERHORN have demonstrated improved benefit with ICIs. Pancreatic cancer, characterized by its immunologically "cold" microenvironment, has shown limited response to immunotherapy. However, strategies that combine immune checkpoint inhibitors with chemotherapy have shown some early results. In colorectal cancer, microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) tumors exhibit strong responses to ICIs, while ongoing trials aim to refine treatment for microsatellite-stable (MSS) cases. For hepatocellular carcinoma (HCC), immunotherapy combinations are regarded as a first-line treatment due to its efficacy over traditional chemotherapy. Cholangiocarcinoma (CCA) lacks pre-surgical tumor reduction options and neoadjuvant therapies, but the results of TOPAZ-1 showed that a combination of durvalumab, gemcitabine, and cisplatin improved overall survival in the advanced setting. Lastly, immunotherapy is emerging as a viable option for advanced forms of anal cancer, with trials exploring checkpoint inhibitors and adoptive cell therapies. Despite the progress, challenges such as tumor heterogeneity and immunosuppressive microenvironments necessitate ongoing research to optimize immunotherapeutic strategies. <h3>Synopsis</h3> Immunotherapy has revolutionized gastrointestinal cancer treatment, with immune checkpoint inhibitors showing promise in esophageal, colorectal, and hepatobiliary cancers. However, challenges including tumor heterogeneity and immunosuppressive microenvironments persist. This manuscript highlights advancements, limitations, and future strategies in integrating immunotherapy across diverse gastrointestinal malignancies, emphasizing the need for innovative approaches to optimize outcomes.