胰腺癌中的肿瘤内微生物组失衡会促进耐受性免疫反应并引发免疫治疗耐药性。在这里，我们展示了配备镓多酚网络 (LGG@Ga-poly) 的鼠李糖乳杆菌 GG 益生菌，通过调节微生物群-免疫相互作用来支持胰腺癌的免疫治疗。口服给药后，LGG@Ga-poly专门针对胰腺肿瘤，并通过镓促进的细菌铁呼吸破坏选择性地根除促进肿瘤的变形菌和微生物衍生的脂多糖。肿瘤内微生物群的消除会阻碍肿瘤 Toll 样受体的激活，从而减少肿瘤细胞的免疫抑制性 PD-L1 和白细胞介素 1β 表达，减少免疫耐受性骨髓细胞群，并改善肿瘤中细胞毒性 T 淋巴细胞的浸润。此外，LGG@Ga-poly 在预防和治疗方面均能抑制胰腺肿瘤的生长，并在雌性小鼠临床前癌症模型中增强免疫检查点阻断的抗肿瘤功效。总体而言，我们提供的证据表明，精心设计的针对肿瘤内微生物群的生物材料可以有效增强具有挑战性的胰腺癌的免疫治疗。© 2024。作者。

The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with a gallium-polyphenol network (LGG@Ga-poly), bolster immunotherapy in pancreatic cancer by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets pancreatic tumors specifically, and selectively eradicates tumor-promoting Proteobacteria and microbiota-derived lipopolysaccharides through a gallium-facilitated disruption of bacterial iron respiration. This elimination of intratumor microbiota impedes the activation of tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 and interleukin-1β expression by tumor cells, diminishing immunotolerant myeloid populations, and improving the infiltration of cytotoxic T lymphocytes in tumors. Moreover, LGG@Ga-poly hampers pancreatic tumor growth in both preventive and therapeutic contexts, and amplifies the antitumor efficacy of immune checkpoint blockade in preclinical cancer models in female mice. Overall, we offer evidence that thoughtfully designed biomaterials targeting intratumor microbiota can efficaciously augment immunotherapy for the challenging pancreatic cancer.© 2024. The Author(s).