The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8⁺ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8⁺ T cell recruitment through the CXCL10–CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8⁺ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

肠道微生物群在塑造免疫治疗结果中的关键作用促使对潜在调节剂的研究。在这里，我们表明口服阿卡波糖显着增加了雌性荷瘤小鼠对抗 PD-1 治疗的反应。阿卡波糖调节肠道菌群组成和色氨酸代谢，从而促进趋化因子表达的变化和肿瘤内 T 细胞浸润的增加。我们将 CD8⁺ T 细胞确定为决定联合疗法疗效的关键成分。进一步的实验表明，阿卡波糖通过 CXCL10-CXCR3 通路促进 CD8⁺ T 细胞募集。粪便微生物群移植和肠道微生物群耗竭测定表明，阿卡波糖的作用取决于肠道微生物群。具体来说，阿卡波糖通过色氨酸分解代谢物吲哚乙酸酯增强抗 PD-1 治疗的疗效，促进 CXCL10 表达，从而促进 CD8⁺ T 细胞募集，使肿瘤对抗 PD-1 治疗敏感。阿卡波糖富含的婴儿双歧杆菌也改善了对抗 PD-1 治疗的反应。总之，我们的研究支持阿卡波糖和抗 PD-1 联合用于癌症免疫治疗的潜在组合。