Journal
CANCER IMMUNOLOGY RESEARCH
Volume 8, Issue 10, Pages 1243-1250Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-20-0196
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Funding
- JSPS KAKENHI [JP19K16820]
- H2020 ONCOBIOME
- Ligue contre le Cancer
- Agence Nationale de la Recherche (ANR) [ANR-19-CE15-0029]
- Association pour la recherche sur le cancer
- Canceropole Ile-de-France
- Fondation pour la Recherche Medicale
- Fondation Carrefour
- Institut National du Cancer
- Inserm (HTE)
- LabEx Immuno-Oncology
- RHU Torino Lumiere [ANR-16-RHUS-0008]
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- FHU CARE, Dassault, and Badinter philantropia
- Paris Alliance of Cancer Research Institutes
- Agence Nationale de la Recherche (ANR) [ANR-19-CE15-0029] Funding Source: Agence Nationale de la Recherche (ANR)
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The gut microbiome (GM) plays an important role in shaping systemic immune responses and influences immune checkpoint inhibitor (ICI) efficacy. Antibiotics worsen clinical outcomes in patients receiving ICI. However, whether GM profiling and baseline antibiotic can be a biomarker of ICI efficacy in advanced non-small cell lung cancer (NSCLC) remains unknown. We prospectively collected baseline (pre-ICI) fecal samples and clinical data of 70 Japanese patients suffering from advanced NSCLC and treated them with anti-PD-1/PD-L1 antibodies as a first-line or treatment-refractory therapy. We performed 16S rRNA V3-V4 sequencing of gene amplicons of fecal samples, and bacteria diversity and differential abundance analysiswas performed. The clinical endpointswere objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAE). ORR was 34%, and median PFS and OS were 5.2 and 16.2 months, respectively. Patients who received pre-ICI antibiotic had lower alpha diversity at baseline and underrepresentation of Ruminococcaceae UCG 13 and Agathobacter. When analyzing antibiotic-free patients, alpha diversity correlated with OS. In addition, Ruminococcaceae UCG 13 and Agathobacter were enriched in patients with favorable ORR and PFS >6 months. Ruminococcaceae UCG 13 was enriched in patients with OS > 12 months. GM differences were observed between patients who experienced low- versus high-grade irAE. We demonstrated the negative influence of antibiotic on the GM composition and identified the bacteria repertoire in patients experiencing favorable responses to ICI.
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