Abstract
Gastrointestinal tumors are characterized by high global incidence and mortality rates. Although immune checkpoint inhibitors (ICIs) have achieved breakthroughs in some of these cancers, their overall response rate remains low. Neoantigen cancer vaccines have emerged as a promising new strategy for immunotherapy in gastrointestinal tumors due to their high specificity and strong immunogenicity. These vaccines effectively activate specific T-cell immunity and can produce synergistic effects when combined with ICIs. Various vaccine platforms offer distinct advantages, and clinical trials have shown encouraging potential in inducing immune responses and extending progression-free survival. Meanwhile, current challenges and future directions cannot be ignored. Key challenges primarily involve the accuracy of neoantigen prediction, tumor heterogeneity, and optimal treatment timing. Future directions include artificial intelligence (AI)-assisted multi-omics screening, the development of universal vaccines, optimization of novel delivery systems, and multimodal combination strategies. These advances are expected to promote the application of neoantigen cancer vaccines in postoperative recurrence prevention and early-stage treatment, ultimately moving toward personalized precision immunotherapy. This article systematically reviews the clinical progress and prospects of neoantigen cancer vaccines in treating gastrointestinal tumors, aiming to provide insights for immunotherapy in this field and offer new perspectives for further optimization of such vaccines.