肠道微生物群影响对免疫检查点抑制剂 (ICI) 的反应。高水平的普拉梭菌与多种癌症类型对 ICI 的阳性反应相关。在这里，基于粪便鸟枪法宏基因组学数据，我们在两个独立的非小细胞肺癌和晚期黑色素瘤患者队列中显示，基线时高水平的普拉梭菌与 ICI 的更好临床反应呈正相关。在 MCA205 荷瘤小鼠中，给予已处于炎症性肠病临床开发阶段的 F. prausnitzii 菌株 EXL01，可在临床和肿瘤转录组水平上在抗生素诱导的微生物群扰动的背景下恢复对 ICI 的抗肿瘤反应。在体外，EXL01 菌株在 ICI 存在的情况下增强 T 细胞活化。有趣的是，口服 EXL01 菌株不会引起粪便微生物群多样性或组成的任何变化，表明对小肠免疫细胞有直接影响。 F. prausnitzii 菌株 EXL01 将在不久的将来作为 ICI 佐剂在多种癌症中进行评估。© 2024 作者。经泰勒许可出版

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of F. prausnitzii at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of F. prausnitzii strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.