Galectin-9 and Tim-3 Contribute to Immune Evasion in Gastric Cancer

New research from the Pontificia Universidad Catolica de Chile has shed light on the role of galectin-9 and Tim-3 in gastric cancer. Investigators found that both galectin-9 and Tim-3 are upregulated in gastric tumors and associated with poor patient survival. Galectin-9 was found to promote Treg suppressive activity and CD8 T cell dysfunction ex vivo through Tim-3 engagement, independently of PD-1 signaling. The study's findings suggest that galectin-9 contributes to immune evasion in GC by promoting Treg expansion and CD8 T cell exhaustion, potentially driving resistance to anti-PD-1 therapy.

Key Takeaways:

• Galectin-9 and Tim-3 are upregulated in gastric tumors and associated with poor patient survival.
• Galectin-9 promotes Treg suppressive activity and CD8 T cell dysfunction ex vivo through Tim-3 engagement.
• The study suggests that galectin-9 contributes to immune evasion in GC by promoting Treg expansion and CD8 T cell exhaustion.
• The findings suggest that circulating galectin-9 may be a candidate biomarker of anti-PD-1 resistance.
• Combined blockade of PD-1 and Tim-3 may enhance immunotherapeutic efficacy in GC.

Statistics:

• 16% of gastric tumors had upregulated expression of both LGALS9 and HAVCR2 (Source: Frontiers in Immunology).
• Patients with high LGALS9 expression had poor survival rates (Source: Frontiers in Immunology).
• 58% of CD8 T cells were dysfunctional in patients with high LGALS9 expression (Source: Frontiers in Immunology).

Sources:

• Galectin-9 and Tim-3 in gastric cancer: a checkpoint axis driving T cell exhaustion and Treg-mediated immunosuppression independently of anti-PD-1 blockade. Frontiers in Immunology, 2025,16.
• Cancer Weekly. July 15, 2025; p 719.