The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium,Clostridium butyricumMIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients receivedClostridium butyricumtherapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.
肠道菌群已成为免疫检查点抑制剂（ICI）疗效的关键调节因子。通过靶向重构菌群以增强癌症治疗效果的治疗方法已引起广泛关注。单一活菌生物治疗菌株——丁酸梭菌MIYAIRI 588株（CBM588），已被证实能增强晚期肺癌患者ICI单药治疗的疗效。然而，CBM588是否影响肺癌化疗免疫联合治疗的疗效尚不明确。我们假设CBM588能增强化疗免疫联合治疗的效果，并恢复因使用导致菌群失调药物而疗效下降的非小细胞肺癌（NSCLC）患者的治疗效果。为验证这一假设，我们回顾性分析了106例连续接受化疗免疫联合治疗的IV期或复发性转移性NSCLC患者。采用倾向评分逆概率加权（IPTW）的单变量和多变量Cox比例风险模型进行生存分析。45%的患者接受了丁酸梭菌治疗。CBM588显著延长了接受化疗免疫联合治疗的NSCLC患者的总生存期。CBM588对化疗免疫联合治疗疗效的积极影响因肿瘤程序性死亡配体1（PD-L1）表达水平而异：在PD-L1<1%队列中，CBM588带来的生存获益高于PD-L1 1-49%和PD-L1≥50%队列。此外，在接受质子泵抑制剂和/或抗生素治疗的患者中，CBM588与总生存期的改善相关。CBM588对共生菌群的调控可能增强化疗免疫联合治疗的疗效，值得进一步探索CBM588与免疫治疗之间的协同作用。
肿瘤(癌症)患者之家