The performance of immune-checkpoint inhibitors, which benefit only a subset of patients and can cause serious immune-related adverse events, underscores the need for strategies that induce T-cell immunity with minimal toxicity. The gut microbiota has been implicated in the outcomes of patients following cancer immunotherapy, yet manipulating the gut microbiome to achieve systemic antitumour immunity is challenging. Here we show in multiple murine tumour models that inulin—a widely consumed dietary fibre—formulated as a ‘colon-retentive’ orally administered gel can effectively modulate the gut microbiome in situ, induce systemic memory-T-cell responses and amplify the antitumour activity of the checkpoint inhibitor anti-programmed cell death protein-1 (α-PD-1). Orally delivered inulin-gel treatments increased the relative abundances of key commensal microorganisms and their short-chain-fatty-acid metabolites, and led to enhanced recall responses for interferon-γ⁺CD8⁺ T cells as well as to the establishment of stem-like T-cell factor-1⁺PD-1⁺CD8⁺ T cells within the tumour microenvironment. Gels for the in situ modulation of the gut microbiome may be applicable more broadly to treat pathologies associated with a dysregulated gut microbiome.

免疫检查点抑制剂的性能仅使一小部分患者受益，并可能导致严重的免疫相关不良事件，这凸显了需要以最小的毒性诱导 T 细胞免疫的策略。肠道微生物群与癌症免疫治疗后患者的预后有关，但操纵肠道微生物群以实现全身抗肿瘤免疫具有挑战性。在这里，我们在多个小鼠肿瘤模型中表明，菊粉（一种广泛食用的膳食纤维）被配制为“结肠保留”口服凝胶，可以有效地原位调节肠道微生物组，诱导全身记忆 T 细胞反应并增强抗肿瘤活性检查点抑制剂抗程序性细胞死亡蛋白-1 (α-PD-1)。口服菊粉凝胶治疗增加了关键共生微生物及其短链脂肪酸代谢物的相对丰度，并增强了干扰素-γ ⁺ CD8 ⁺ T细胞的回忆反应以及干细胞样细胞的建立。肿瘤微环境中的 T 细胞因子 1 ⁺ PD-1 ⁺ CD8 ⁺ T 细胞。用于原位调节肠道微生物组的凝胶可能更广泛地适用于治疗与肠道微生物组失调相关的病理。