Despite overall success, T cell checkpoint inhibitors for cancer treatment are still only efficient in a minority of patients. Recently, intestinal microbiota was found to critically modulate anti-cancer immunity and therapy response. Here, we identify Clostridiales members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC). Interestingly, these commensal species are also significantly reduced in CRC patients compared with healthy controls. Oral application of a mix of four Clostridiales strains (CC4) in mice prevented and even successfully treated CRC as stand-alone therapy. This effect depended on intratumoral infiltration and activation of CD8⁺ T cells. Single application of Roseburia intestinalis or Anaerostipes caccae was even more effective than CC4. In a direct comparison, the CC4 mix supplementation outperformed anti-PD-1 therapy in mouse models of CRC and melanoma. Our findings provide a strong preclinical foundation for exploring gut bacteria as novel stand-alone therapy against solid tumors.

尽管总体上取得了成功，但用于癌症治疗的 T 细胞检查点抑制剂仍然只对少数患者有效。最近，人们发现肠道微生物群可以严重调节抗癌免疫和治疗反应。在这里，我们确定了与结肠直肠癌 (CRC) 小鼠模型中较低的肿瘤负荷相关的肠道微生物群的梭菌属成员。有趣的是，与健康对照相比，CRC 患者的这些共生物种也显着减少。在小鼠中口服应用四种梭菌属菌株 (CC4) 的混合物可预防甚至成功地将 CRC 作为独立疗法进行治疗。这种作用取决于肿瘤内浸润和 CD8 ⁺ T 细胞的激活。单次申请Roseburia gutis或Anaerostipes caccae甚至比 CC4 更有效。在直接比较中，CC4 混合补充剂在 CRC 和黑色素瘤小鼠模型中的表现优于抗 PD-1 疗法。我们的研究结果为探索肠道细菌作为针对实体瘤的新型独立疗法提供了强有力的临床前基础。