Synergistic Potential of Phytochemicals and Immune Checkpoint Inhibitors in Gastrointestinal Cancer Therapy

Gastrointestinal (GI) cancers, including those of the esophagus, stomach, liver, pancreas, and colon, remain a major cause of cancer-related deaths worldwide due to delayed diagnosis and limited therapeutic success. Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating antitumor immunity, their benefits in GI cancers are often restricted by poor response rates, immune-related side effects, and acquired resistance. Phytochemicals, naturally occurring compounds from plants, have emerged as promising adjuncts capable of enhancing ICI efficacy. They modulate key immune pathways, including PD-1/PD-L1 signalling, and influence oxidative stress, cytokine release, and tumor microenvironment remodelling. By targeting multiple signalling cascades, phytochemicals can strengthen immune responses and reduce therapy-associated toxicity. This chapter discusses the synergistic potential of combining phytochemicals with ICIs, focusing on their mechanisms of action and prospects for developing more effective and personalized immunotherapeutic strategies for GI cancer management.