靶向天冬酰胺通过增强 CD8(+) T 细胞抗肿瘤反应增强胃癌抗 PD-L1 免疫治疗

The therapeutic efficacy of asparagine targeting was evaluated in GC tumor models. CD8+ T cell populations within the TME were analyzed by flow cytometry, while cytokine and chemokine levels (IFN-γ, GZMB, CXCL9, CXCL10) were quantified by ELISA. The effects on CD8+ T cell activation and antitumor function were assessed in vitro and in vivo. Synergistic efficacy with anti-PD-L1 therapy was evaluated in GC models, and the dependency on CD8+ T cells was confirmed via antibody-mediated depletion experiments.

Targeting asparagine inhibited GC growth in vitro and in vivo, implicating immune system involvement. Mechanistically, asparagine targeting significantly increased the proportion of CD8+ T cells within the TME and upregulated the expression of IFN-γ, GZMB, CXCL9, and CXCL10. Furthermore, combining asparagine targeting with anti-PD-L1 therapy produced synergistic antitumor activity. This combined therapeutic effect was significantly attenuated by the depletion of CD8+ T cells. DISCUSSION: Our findings indicate that targeting asparagine promotes CD8+ T cell activation and infiltration, thereby remodeling the GC immune microenvironment to enhance host antitumor immunity. The combination of asparagine targeting with anti-PD-L1 therapy elicits potent, synergistic antitumor effects that are demonstrably dependent on CD8+ T cells. This study provides a strong rationale for targeting asparagine metabolism as a novel strategy to improve immunotherapeutic outcomes in GC.