The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping the response to and toxicity from ICIs, prompting the need for further studies in this area.

肠道微生物群决定了癌症对免疫检查点抑制剂 (ICI) 的反应，但饮食和地理影响尚未在前瞻性试验中得到充分研究。为了解决这个问题，我们前瞻性地分析了来自澳大利亚和荷兰的 103 名接受新辅助 ICI 治疗高风险可切除转移性黑色素瘤的试验患者的基线肠道（粪便）微生物群特征和饮食模式，并对 115 名接受 ICI 治疗的黑色素瘤患者的数据进行了综合分析美国的 ICI。我们观察了反应和免疫相关不良事件 (irAE) 的地理上不同的微生物特征。总体而言，以瘤胃球菌科为主的微生物组的反应率高于拟杆菌科- 主导的微生物组。不良反应与较低的纤维和 omega 3 脂肪酸消耗以及基线时外周循环中 C 反应蛋白水平升高有关。总之，这些数据提供了对天然肠道微生物群特征、饮食摄入和全身炎症在形成 ICIs 反应和毒性方面的相关性的深入了解，促使需要在该领域进行进一步研究。