Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
J Transl Med. 2024 Apr 2;22(1):326. doi: 10.1186/s12967-024-05135-5.
The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown.
We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy.
The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites.
The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.
肠道微生物群和代谢物对晚期表皮生长因子受体（EGFR）野生型非小细胞肺癌（NSCLC）患者对免疫检查点抑制剂（ICI）反应的影响已被研究。然而，它们对 EGFR 突变（EGFR+）NSCLC 的影响尚不清楚。
我们前瞻性地记录了晚期 EGFR+NSCLC 患者的临床病理特征，并评估了使用抗生素或益生菌与免疫治疗疗效之间的潜在关联。在基线、早期治疗、反应和进展状态时采集粪便样本，并进行宏基因组下一代测序和超高效液相色谱-质谱分析，以评估肠道微生物群和代谢物对免疫治疗疗效的影响。
74 例晚期 EGFR+NSCLC 患者的临床数据完整，18 例患者的粪便样本动态采集。使用抗生素的患者无进展生存期（mPFS，4.8 个月 vs. 6.7 个月；P=0.037）更短；益生菌对 PFS 没有影响。在免疫治疗过程中鉴定出两种动态类型的肠道微生物群：一种类型在反应时间点的相对丰度最低，另一种类型在反应时间点的丰度最高。代谢组学显示应答者和无应答者之间代谢物分布存在显著差异。脱氧胆酸、甘油和喹啉酸在应答者中富集，而 L-瓜氨酸在无应答者中富集。肠道微生物群和代谢物之间存在显著相关性。
抗生素的使用削弱了晚期 EGFR+NSCLC 患者免疫治疗的疗效。肠道微生物群和代谢物的分布特征和动态变化可能预示着晚期 EGFR+NSCLC 免疫治疗的疗效。
