Journal article
Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer
Journal of clinical oncology, Vol.39(15_suppl), pp.e21024-e21024
05/20/2021
DOI: 10.1200/JCO.2021.39.15_suppl.e21024
Abstract
e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.
Details
- Title: Subtitle
- Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer
- Creators
- Justin Chau - University of Iowa Hospitals and Clinics, Iowa City, IAMeeta Yadav - University of Iowa Hospitals and Clinics, Iowa City, IABen Liu - University of Kansas, Lawrence, KSMuhammad Furqan - University of Iowa Hospitals and Clinics, Iowa City, IAQun Dai - University of Kansas Medical Center, Kansas City, KSShailesh Shahi - University of Iowa Hospitals and Clinics, Iowa City, IAArnav Gupta - University of Iowa Hospitals and Clinics, Iowa City, IAKeri Nace Mercer - University of Iowa Hospitals and Clinics, Iowa City, IAEvan Eastman - University of Iowa Hospitals and Clinics, Iowa City, IATaher Abu Hejleh - University of Iowa Hospitals and Clinics, Iowa City, IACarlos Hou Fai Chan - University of Iowa Hospitals and Clinics, Iowa City, IAGeorge J Weiner - University of Iowa Hospitals and Clinics, Iowa City, IACatherine Cherwin - University of Iowa College of Nursing, Iowa City, IASonny T.M Lee - Kansas State University, Manhattan, KSCuncong Zhong - University of Kansas, Lawrence, KSAshutosh Mangalam - University of Iowa Hospitals and Clinics, Iowa City, IAJun Zhang - University of Kansas Medical Center, Kansas City, KS
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.39(15_suppl), pp.e21024-e21024
- DOI
- 10.1200/JCO.2021.39.15_suppl.e21024
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Holden Comprehensive Cancer Center Enhancement Grant; name: Other Foundation; DOI: 10.13039/100000002, name: U.S. National Institutes of Health; name: University of Kansas Startup Fund; Margaret Heppelmann and Michael Wace; Play with a Pro Lung Cancer Research Fund
- Language
- English
- Date published
- 05/20/2021
- Academic Unit
- Surgery; Internal Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; Dental Research; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Pathology; Nursing
- Record Identifier
- 9984084133102771
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