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Qun Dai



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-18 - Analysis of Patient Microbiome and Its Correlation to Immunotherapy Response and Toxicity in Lung Cancer (ID 1301)

      10:15 - 18:15  |  Author(s): Qun Dai

      • Abstract

      Background

      In recent years, attention has shifted to modification of tumor responses to immunotherapy, potentially via the host microbiome. The mechanisms of this association, causative or consequential, remain incompletely understood. We seek to explore this further with a longitudinal study of lung cancer patient microbiomes, outcomes and toxicities preceding and during immunotherapy.

      Method

      Patients with lung cancer (LC) treated with immunotherapy (anti-PD-1/L1 agents including pembrolizumab, nivolumab, atezolizumab and durvalumab) with or without chemotherapy at the University of Iowa were consented for this ongoing study. Subjects from November 2018 – February 2019 were included in this report. Nasal and buccal swabs, as well as stool samples were obtained prior to therapy in compliance with institutional regulatory guidelines. Patients were treated and monitored per respective disease protocol; responses were recorded per RECIST 1.1 criteria, and toxicities graded per CTCAE 5.0. Samples underwent DNA extraction followed by 16S rRNA metagenomic analysis and taxonomic profiling using Divisive Amplicon Denoising Algorithm (DADA)-2 pipeline. The microbiome from all body sites were compared. LC gut microbiomes were also compared to fecal samples provided by healthy control residents (HC), as well as patients with other malignancies such as renal clear cell (RCC). This project is registered in clinicaltrial.gov (NCT03688347).

      Result

      Gut microbiota was significantly different compared to oral and buccal microbiota in all patients. Gut microbiota from 16 LC patients were compared to 8 HC samples. LC patients exhibited drastically different baseline microbiota composition at both the phylum level, including dramatic increases in Firmicutes, Actinobacteria and Verrucomicrobia, and significant decreases in Bacteroidetes, Proteobacteria and Cyanobacteria. We noticed a clear inversion of Firmicutes/Bacteroidetes ratio between HC and LC patients, differences also reflected at the genus level. Interestingly, gut microbiome from 5 RCC patients was strikingly different from HC but exhibit high concordance with those from LC. LC patients who experienced immunotherapy-related toxicities were found to have at baseline markedly more Anaerostipes and Eggerthella relative to HC, and fewer Lachnospira.

      Conclusion

      Our study found promising trends in microbiome constitution whose evaluation will benefit from a larger subject pool as we continue to accrue patients. Compared to HC, we found significant differences in baseline LC gut microbiome at phylum and genus levels, and notable differences when comparing LC patients who suffered immunotherapy-related toxicities to those with none. Our project marks an important first step in a long-term study that could shed new light on the microbiome’s influence on immunotherapy treatment outcomes.