Gut microbiome predicts efficacy and immune-related toxicities of advanced non-small cell lung cancer patients treated with anti-PD-1/PD-L1 Ab-based immunotherapy. Gut microbione from Japanease lung cancer cohort

The gut microbiome (GM) plays an important role in shaping systemic immune responses. Preclinical and clinical data suggest that GM influences anti-PD-1/PD-L1 or -CTLA-4 Ab-mediated anti-cancer responses. Furthermore, there is strong evidence that antibiotics (ATB) worsen clinical outcomes based on multiple retrospective and one prospective studies using immune checkpoint inhibition (ICI). However, whether GM profiling, at baseline or post-ATB, could represent a biomarker of response in advanced non-small cell lung cancer (NSCLC) during ICI therapy remains unknown. Moreover, the relationship between specific gut microbiota and incidence of immune-related adverse events (irAEs) remain to be precisely elucidated. The objective of the present study was to characterize the impact of ATB on specific GM signatures using metagenomics sequencing in a cohort of 70 patients with advanced NSCLC treated with anti-PD-1/anti-PD-L-1. Primary endpoints were to define specific gut microbiota associated with response and non-response, progression-free survival (PFS), overall survival (OS), and irAEs in both patients who received ATB and those who did not receive ATB.

肠道微生物组（gut microbiome, GM）在调控全身免疫应答过程中具有重要作用。临床前及临床研究数据均表明，GM可影响抗PD-1/PD-L1或抗CTLA-4抗体介导的抗肿瘤应答。此外，依托多项回顾性研究及一项采用免疫检查点抑制剂治疗（immune checkpoint inhibition, ICI）的前瞻性研究，已有充分证据证实抗生素（antibiotics, ATB）会恶化患者的临床结局。然而，对于晚期非小细胞肺癌（advanced non-small cell lung cancer, NSCLC）患者，在接受ICI治疗期间，基线状态或抗生素干预后的GM谱是否可作为应答生物标志物，目前仍未明确。此外，特定肠道菌群与免疫相关不良事件（immune-related adverse events, irAEs）发生率之间的关联，尚待精准阐明。本研究旨在通过宏基因组测序技术，对70例接受抗PD-1/抗PD-L1治疗的晚期NSCLC患者队列展开分析，以表征ATB对特定GM特征的影响。本研究的主要终点为：在接受ATB与未接受ATB的患者群体中，明确与应答、无应答、无进展生存期（progression-free survival, PFS）、总生存期（overall survival, OS）及irAEs相关的特定肠道菌群。