肠道微生物群在影响免疫治疗结果中的关键作用促使人们对潜在的调节剂进行研究。在这里，我们发现口服阿卡波糖可显着增加雌性荷瘤小鼠对抗 PD-1 治疗的抗肿瘤反应。阿卡波糖调节肠道微生物群组成和色氨酸代谢，从而导致趋化因子表达的变化和肿瘤内 T 细胞浸润的增加。我们确定 CD8 T 细胞是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 途径促进 CD8 T 细胞招募。粪便微生物群移植和肠道微生物群耗竭试验表明，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增强抗 PD-1 治疗的功效，吲哚乙酸可促进 CXCL10 表达，从而促进 CD8 T 细胞募集，使肿瘤对抗 PD-1 治疗敏感。富含阿卡波糖的婴儿双歧杆菌也能改善抗 PD-1 疗法的反应。总之，我们的研究支持阿卡波糖和抗 PD-1 的潜在组合用于癌症免疫治疗。© 2024。作者，获得 Springer Nature Limited 的独家许可。

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.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.