Shoji Fumihiro, Yamaguchi Masafumi, Okamoto Masaki, Takamori Shinkichi, Yamazaki Koji, Okamoto Tatsuro, Maehara Yoshihiko
Department of Thoracic Surgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
Department of Thoracic Oncology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
Front Mol Biosci. 2022 Oct 24;9:1040424. doi: 10.3389/fmolb.2022.1040424. eCollection 2022.
Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiota status "before" initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiota diversity and composition "during" ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiota diversity or composition with ICI response. At the genus level, the alpha diversity of the gut microbiota was significantly greater in responders ( = 17) than in non-responders ( = 11) (Chao 1, = 0.0174; PD whole tree, = 0.0219; observed species, = 0.0238; Shannon, = 0.0362), while the beta diversity of the gut microbiota was significantly different (principal coordinates analysis, = 0.035). Compositional differences in the gut microbiota were observed between the two groups; in particular, g_ was enriched in responders, whereas o_ was enriched in non-responders. The progression-free survival (PFS) of patients enriched gut microbiota of g_ was significantly longer [median survival time (MST): not reached vs. 549 days, = 0.0480] and the PFS of patients with gut microbiota of o_ was significantly shorter (MST: 49 vs. 757 days, = 0.0205). There were no significant differences between groups in the oral microbiota. This study revealed a strong association between gut microbiota diversity and ICI response in NSCLC patients. Moreover, specific gut microbiota compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response.
包括免疫检查点抑制剂（ICI）在内的癌症免疫疗法彻底改变了非小细胞肺癌（NSCLC）的治疗方式。最近，ICI治疗开始“之前”的微生物群状态已被强调为接受ICI治疗患者的一种预测性生物标志物。然而，ICI治疗“期间”的微生物群多样性和组成尚不清楚。这项多中心、前瞻性观察性研究分析了28例NSCLC患者的唾液和粪便。我们进行了16S核糖体RNA基因测序，然后分析口腔和肠道微生物群多样性或组成与ICI反应之间的关联。在属水平上，应答者（n = 17）的肠道微生物群α多样性显著高于无应答者（n = 11）（Chao 1，P = 0.0174；PD全树，P = 0.0219；观察到的物种，P = 0.0238；香农指数，P = 0.0362），而肠道微生物群的β多样性有显著差异（主坐标分析，P = 0.035）。两组之间观察到肠道微生物群的组成差异；特别是，g_在应答者中富集，而o_在无应答者中富集。g_肠道微生物群富集患者的无进展生存期（PFS）显著更长[中位生存时间（MST）：未达到 vs.549天，P = 0.0480]，而o_肠道微生物群患者的PFS显著更短（MST：49天 vs.757天，P = 0.0205）。口腔微生物群在各组之间没有显著差异。这项研究揭示了NSCLC患者肠道微生物群多样性与ICI反应之间的密切关联。此外，特定的肠道微生物群组成可能会影响ICI反应。这些发现可能有助于识别预测ICI反应的生物标志物。
