Work

Disruption of tissue-resident FOLR2+tumor-associated macrophages-derived interleukin-10 improves anti-PD-1 efficacy in gastric cancer

Year: 2025

Type: article

Abstract: BACKGROUND: Our previous studies have demonstrated monocyte-derived tumour-associated macrophages (TAMs) secret CXCL8, which induces autonomous PD-L1 expression resulting in immune suppressive microenvironment. However, the role of tissue-resident macrophages in gastric cancer remains obscure. METHODS: The study enrolled four cohorts, consisting of two tumor microarrays and two groups of transcriptional data. The associations of FOLR2+TAMs with clinical outcomes and genomic features were analyzed. In vitro culture of fresh tumor tissue was performed to evaluate the potential therapeutic effect of blocking PD-1 and IL-10 in gastric cancer. RESULTS: Increased level of FOLR2+TAMs indicates poor clinical outcome and tumour progression in patients with gastric cancer. High level of FOLR2+TAMs is associated with increased CD8+T cells infiltration. However, FOLR2+TAMs inhibit CD8+T cells function by expressing PD-L1 and IL-10. Finally, we show that disrupting IL-10 sensitises anti-PD-1 blockade and promotes antitumor immunity in FOLR2+TAMshigh tumours. CONCLUSIONS: FOLR2+TAMs contribute to the immunosuppressive microenvironment by expressing PD-L1 and IL-10 in gastric cancer. Combining anti-PD-1 and anti-IL-10 may drive antitumor response in FOLR2+TAMshigh tumours, providing potential therapeutic effects for patients with gastric cancer.

Source: International Journal of Surgery

DOI: 10.1097/js9.0000000000004105