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Due to the high variance in response rates concerning anti-PD1 immunotherapy (IT), there is an unmet need to discover innovative biomarkers to predict immune checkpoint inhibitor (ICI)-efficacy. Our study included 62 Caucasian advanced-stage non-small cell lung cancer (NSCLC) patients treated with anti-PD1 ICI. Gut bacterial signatures were evaluated by metagenomic sequencing and correlated with progression-free survival (PFS), PD-L1 expression and other clinicopathological parameters. We confirmed the predictive role of PFS-related key bacteria with multivariate statistical models (Lasso- and Cox-regression) and validated on an additional patient cohort (n = 60). We find that alpha-diversity showed no significant difference in any comparison. However, there was a significant difference in beta-diversity between patients with long- (>6 months) vs. short (≤6 months) PFS and between chemotherapy (CHT)-treated vs. CHT-naive cases. Short PFS was associated with increased abundance of Firmicutes (F) and Actinobacteria phyla, whereas elevated abundance of Euryarchaeota was specific for low PD-L1 expression. F/Bacteroides (F/B) ratio was significantly increased in patients with short PFS. Multivariate analysis revealed an association between Alistipes shahii, Alistipes finegoldii, Barnesiella visceriola, and long PFS. In contrast, Streptococcus salivarius, Streptococcus vestibularis, and Bifidobacterium breve were associated with short PFS. Using Random Forest machine learning approach, we find that taxonomic profiles performed superiorly in predicting PFS (AUC = 0.74), while metabolic pathways including Amino Acid Synthesis and Fermentation were better predictors of PD-L1 expression (AUC = 0.87). We conclude that specific metagenomic features of the gut microbiome, including bacterial taxonomy and metabolic pathways might be suggestive of ICI efficacy and PD-L1 expression in NSCLC patients. [ABSTRACT FROM AUTHOR]

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO2 coincides with an increase in certain species and the "GABA shunt" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity. [ABSTRACT FROM AUTHOR]

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV. [ABSTRACT FROM AUTHOR]