Tumor microenvironment in gastric cancer immune tolerance and its therapeutic relevance in immunomodulation (Review)

Gastric cancer (GC) is a highly heterogeneous malignancy and the formation of an immunotolerant tumor microenvironment (TME) is an important promoter of tumor progression, treatment resistance and a poor prognosis. The TME is composed of cellular components including immune cells as well as non-cellular elements (such as the extracellular matrix) which induce immune tolerance through numerous mechanisms. Comprehensive exploration of TME regulatory pathways in GC has established the theoretical foundation for targeted immunomodulatory strategies. TME-targeted immunotherapies have demonstrated efficacy in reversing immune tolerance and enhancing antitumor immunity. Additionally, when combined with chemotherapy, radiotherapy and/or targeted agents, these therapies notably improve response rates in patients with GC. The present review evaluates the impact of the TME on the development of immune tolerance in GC and the therapeutic implications of immunomodulation. The components of the GC TME were systematically characterized, and the present review discusses the contributions of cellular components to establishing an immunosuppressive microenvironment, investigates the molecular mechanisms underlying immune tolerance in GC, identifies key immune cells and their crosstalk within the TME and summarizes current treatments targeting TME-mediated immune tolerance, all with the aim to provide insights into optimized immunotherapeutic strategies and improve patient outcomes.