Abstract 1054P
Background
The intratumoral microbiome (IM) associates with immune changes in the tumor microenvironment of preclinical lung cancer models; Escherichia exerts an immunostimulatory effect, reducing lung metastases. In patients (pts) with non-small cell lung cancer (NSCLC), the relationship between the IM and immune checkpoint inhibitor (ICI) efficacy is unknown. We sought to detect intratumoral bacteria in pts with advanced NSCLC using hybrid capture-based, next generation sequencing (NGS).
Methods
All NSCLC pts treated with ICI-based therapy who underwent NGS at our center were included (N=1462). We extracted unmapped reads from processed BAM files (Samtools). Unmapped reads were queried for bacteria using blastn against the NCBI database, excluding contaminants. TCGA lung adenocarcinoma data (non-ICI treated pts) was used for validation and processed via the same pipeline.
Results
1881 bacterial reads were detected/sample (mean). Smoking was associated with lower alpha diversity by Simpson (p<0.001) and Shannon metrics (p<0.001). Diversity was similar between pts with/without a driver alteration, and across histologies. Intratumoral Escherichia was associated with better PFS (HR 0.70, 95%CI 0.6-0.9, p<0.001), and OS (HR 0.75, 95% CI 0.61-0.94, p=0.01) in pts treated with single-agent ICI, but not combination Chemo/ICI. Intratumoral Escherichia was not associated with PDL1% by IHC or mutational burden (Spearman). After adjusting for prognostic features, the presence of Escherichia in the tumor sample was associated with better PFS (p=0.02) in pts treated with single-agent ICI. In the TCGA cohort (N=294 samples), 522 reads were detected/sample and smoking was also associated with decreased alpha diversity (Gini Simpson, p=0.003); Shannon, p=0.012), while Escherichia was not associated with outcomes.
Conclusions
We define the intratumoral microbiome using unmapped reads via a novel hybrid capture NGS method from two independent cohorts and show an association of intratumoral Escherichia with progression-free survival, which was specific to single-agent ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Elkrief: Financial Interests, Institutional, Funding: Canadian Institutes of Health Research, Royal College of Surgeons and Physicians of Canada, Henry R. Shibata Cedars Cancer Foundation Scholarship. M. Hellmann: Financial Interests, Personal and Institutional, Funding: grants from BMS; and personal fees from Achilles; Adagene; Adicet; Arcus; AstraZeneca; Blueprint; BMS; DaVolterra; Eli Lilly; Genentech/Roche; Genzyme/Sanofi; Janssen; Immunai; Instil Bio; Mana Therapeutics; Merck; Mirati; Natera; Pact Pharma; Shattuck La. A.J. Schoenfeld: Financial Interests, Personal and Institutional, Funding: reports consulting/advising role to J&J, KSQ therapeutics, BMS, Enara Bio, Perceptive Advisors, and Heat Biologics. Research funding: GSK (Inst), PACT pharma (Inst), Iovance Biotherapeutics (Inst), Achilles therapeutics (Inst), Merck (Inst), BMS (Inst), H. M. Ladanyi: Financial Interests, Personal and Institutional, Funding: Honoraria - Merck (I) Consulting or Advisory Role - Bayer; Bristol-Myers Squibb; Merck (I); NCCN/AstraZeneca; Takeda Research Funding - Helsinn Therapeutics; Loxo (Inst). C.M. Vanderbilt: Financial Interests, Personal, Funding: have equity interest in Paige AI and a consultant (without compensation). All other authors have declared no conflicts of interest.