Recent advances in tumour microenvironment impact immunotherapy resistance in gastric cancer.

Abstract

Gastric cancer (GC) is one of the most common malignant tumours worldwide, and its high morbidity and mortality are closely related to insignificant early symptoms, diagnosis mostly at an advanced stage and immunotherapy resistance. In recent years, the application of immunotherapy, especially immune checkpoint inhibitors, has brought new hope for treating GC; however, the problem of drug resistance is still a major challenge. The clinical need for effective immunotherapy in GC is still unmet, as the majority of patients do not respond to current treatments or develop resistance over time. The tumour microenvironment (TME) is a key factor affecting immunotherapy resistance. It contains immunosuppressive cells, cancer-associated fibroblasts, the extracellular matrix, immunosuppressive cytokines and other components, which interact to form an immunosuppressive environment and weaken the effect of immunotherapy. In addition, tumour metabolic reprogramming further promotes immune resistance by affecting immune cell function and activity. However, the detailed mechanisms by which these components drive resistance are not fully understood, and there is a significant gap in the literature regarding comprehensive strategies to overcome this resistance. This review aims to address this gap by elucidating how key components of the TME contribute to immunotherapy resistance in GC. The study reviews the effect of key components in the TME of GC on immunotherapy resistance and its mechanism and discusses potential treatment strategies and future research directions for these mechanisms; it provides a theoretical basis for overcoming immunotherapy resistance and improving the prognosis of patients with GC.