Multifaceted roles of chemokines in gastric cancer: From tumor microenvironment modulation to therapeutic targeting (Review)

Abstract

Gastric cancer (GC) is a malignant solid tumor with limited treatment options, particularly for advanced tumor stages. Chimeric antigen receptor (CAR)-T therapy has been successful in treating hematological malignancies; however, its efficacy in solid tumors remains suboptimal due to the complex tumor microenvironment (TME). The TME in GC comprises diverse signaling molecules and cellular components, including fibroblasts, immune cells and stromal proteins; these components can support tumor growth, invasion and immune evasion. In the GC TME, the dynamic interactions between cytokines, chemokines, growth factors and their receptors can foster chronic inflammation and immunosuppression, thereby facilitating tumor progression, metastasis and therapeutic resistance. The present review provides novel insights into the understanding and functional impact of cell-chemokine interaction networks in GC, highlighting the therapeutic implications of chemokines in immunotherapy. In addition, current related research areas are outlined and advances in therapeutic strategies targeting key chemokine signaling pathways are discussed. By providing critical insights into TME reprogramming and immunomodulation, the current study aims to encourage the strategic application of chemokine engineering in next-generation CAR-T immunotherapy for GC.