Microbiota biomarkers as predictors on immunotherapy response in patients with advanced non-small cell lung cancer

INTRODUCTION: Intratumoral microbiota is being investigated as a potential biomarker in cancer. In this study, we investigated tissue microbiota in advanced non-small cell lung cancer (NSCLC) to evaluate response to immune checkpoint inhibitors (ICIs). MATERIAL AND METHODS: We performed a retrospective study in 41 tumor tissues from patients with advanced NSCLC treated with ICI +/- chemotherapy. Microbial profiling was analyzed through 16S rRNA amplicon sequencing using Ion Torrent technology. Bioinformatic analysis was performed with the QIIME2 pipeline. RESULTS: Cox and logistic regression identified two bacterial consortia with prognostic relevance in terms of overall survival (OS), progression-free survival (PFS) and treatment response: the KBUBe score, which included four genera (Klebsiella, Brevundimonas, Undibacterium and Beijerinckiaceae), and the OSAA score, which comprised Olsenella, Salinarimonas, Actinobacillus and Lachnospiraceae genus A2. KBUBe and OSAA scores were significant predictors of OS (hazard ratio [HR] = 0.501, p = 0.009 and HR = 0.491, p < 0.001, respectively) and PFS (HR = 0.579, p = 0.040 and HR = 0.133, p < 0.001, respectively), outperforming PD-L1 expression, ECOG performance status or neutrophil-to-lymphocyte ratio. All patients with the highest KBUBe score were responders, compared with 50% in the lowest-score group (p = 0.035). Similarly, 83.8% of patients with the highest OSAA score were responders, whereas no responders were observed in the lowest-score group (p = 0.001). These findings were confirmed by internal validation and were not confounded by tobacco smoking status, type of therapy and histology. CONCLUSION: Intratumoral microbial communities are associated with survival and treatment response in ICI-treated NSCLC. The KBUBe and OSAA scores represent novel, independent prognostic biomarkers, warranting validation in larger cohorts.