Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.

Gastric cancer ranks among the most prevalent malignant tumors globally, with its immunotherapeutic efficacy constrained by the intricate tumor microenvironment (TME). This review provides a systematic elucidation of the dynamic interaction axis of "nutrient competition-metabolic crosstalk-immunosuppression" within the TME of gastric cancer, approached from a network perspective. Initially, the hypoxic, acidic, and nutrient-deficient conditions of the TME establish a metabolic pressure foundation, compelling cancer and immune cells to engage in intense competition for essential nutrients, thereby inducing a state of metabolic deprivation in effector T cells. Subsequently, this competitive dynamic results in the accumulation of immunosuppressive metabolites, including lactic acid, adenosine, kynurenine, and prostaglandin E2. These metabolites, rather than being mere waste products, form a complex metabolic crosstalk network that actively suppresses effective immune function and reshapes the immunosuppressive niche through mechanisms such as receptor signaling and epigenetic modification. Ultimately, this multi-layered metabolic reprogramming network collectively facilitates immune evasion and resistance to immunotherapy in gastric cancer. A comprehensive analysis of the network is anticipated to furnish a vital theoretical foundation for the development of novel therapeutic strategies. These strategies may include targeting pivotal metabolic nodes, alleviating immunosuppression, and integrating immune checkpoint blockade, all of which are expected to enhance the clinical prognosis of patients with gastric cancer.