Characterizing the tumor microbiome of non-small cell lung cancer patients receiving neoadjuvant chemo-immunotherapy (SAKK 16/14)

<bold>Introduction:</bold> The host microbiome is critical for checkpoint inhibitor (CPI) efficacy. Newer data suggest that the tumor-co-localized microbiome is critical for CPI efficacy as well, thus extending the role of microbes beyond the gut compartment. Here, we characterized the tumor-co-localized microbiome of non-small cell lung cancer (NSCLC) patients receiving neoadjuvant chemo-immunotherapy. <bold>Methods:</bold> 53 samples from 48 patients of the SAKK 16/14 trial (<ext-link>NCT02572843</ext-link>), a phase II study showing safety and efficacy of durvalumab addition to neoadjuvant chemotherapy in resectable NSCLC, were analyzed using 16S rRNA-based bacterial identification. 16 pre-treatment biopsies and 37 resection specimens were analyzed. Operational taxonomic units were defined and correlated to clinical characteristics. <bold>Results:</bold> Both pre-treatment biopsies and resection specimens harbored a broad spectrum of bacteria including Proteobacteria, Bacteroidetes and Firmicutes members. Shannon index analytics suggested that the diversity of biopsies (1.36) and resection specimens (1.23) was comparable. Cox proportional hazards models suggested potential associations of certain bacteria with survival, including an Alphaproteobacterium species whose presence was correlated to shorter event-free survival (p<0.05). <bold>Conclusion:</bold> We demonstrate the feasibility of 16S rRNA-based bacterial identification in biopsy and resection samples of NSCLC patients treated with neoadjuvant chemotherapy. Preliminary analyses suggested robustness of bacterial diversity during neodjuvant chemo-immunotherapy. Certain NSCLC-co-localized bacteria were correlated to patient survival, suggesting clinical relevance.