Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.
免疫检查点抑制剂已被提议作为非小细胞肺癌不同阶段多种适应症的标准治疗方案。然而，并非所有患者都能从这些治疗中获益，且部分患者会出现免疫相关不良事件。尽管寻找这些药物疗效预测因子是当前研究的重要领域，相关问题仍未得到解决。有假说认为微生物群可能在调节癌症治疗反应中发挥关键作用；但肠道通透性这一人体因素也需纳入考量，因其与宿主-微生物群相互作用的调控密切相关。本文分析了免疫检查点抑制剂疗效与免疫相关不良事件发生、肠道微生物群状态及肠黏膜通透性之间的潜在关联。作为创新性探索，我们还检测了粪便中短链脂肪酸含量。尽管相关性分析未能确定预测性生物标志物（即使整合所有变量），但研究显示患者的肠道微生物生态系统丰富多样，且肠道屏障完整性保持良好。这些结果为微生物群组成及其与屏障通透性、短链脂肪酸的关联提供了新认知，同时表明在将这些潜在生物标志物纳入免疫检查点抑制剂治疗的临床管理前，仍需开展更多深入研究。
肿瘤(癌症)患者之家