The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non-Small Cell Lung Cancer
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...
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| Published in | Cancer immunology research Vol. 8; no. 10; p. 1243 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.10.2020
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| Online Access | Get more information |
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| Abstract | 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 analysis was performed. The clinical endpoints were 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
UCG 13 and
When analyzing antibiotic-free patients, alpha diversity correlated with OS. In addition,
UCG 13 and
were enriched in patients with favorable ORR and PFS >6 months.
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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| AbstractList | 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 analysis was performed. The clinical endpoints were 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
UCG 13 and
When analyzing antibiotic-free patients, alpha diversity correlated with OS. In addition,
UCG 13 and
were enriched in patients with favorable ORR and PFS >6 months.
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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| Author | Okuma, Yusuke Derosa, Lisa Zitvogel, Laurence Richard, Corentin Routy, Bertrand Terrisse, Safae Elkrief, Arielle Mimpen, Iris Hakozaki, Taiki Hosomi, Yukio Benlaïfaoui, Myriam |
| Author_xml | – sequence: 1 givenname: Taiki orcidid: 0000-0002-9980-4417 surname: Hakozaki fullname: Hakozaki, Taiki organization: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo City, Tokyo, Japan – sequence: 2 givenname: Corentin surname: Richard fullname: Richard, Corentin organization: University of Montreal Research Center (CRCHUM), Montreal, Quebec, Canada – sequence: 3 givenname: Arielle surname: Elkrief fullname: Elkrief, Arielle organization: Segal Cancer Centre, Jewish General Hospital, Department of Oncology, Montreal, Quebec, Canada – sequence: 4 givenname: Yukio surname: Hosomi fullname: Hosomi, Yukio organization: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo City, Tokyo, Japan – sequence: 5 givenname: Myriam surname: Benlaïfaoui fullname: Benlaïfaoui, Myriam organization: University of Montreal Research Center (CRCHUM), Montreal, Quebec, Canada – sequence: 6 givenname: Iris surname: Mimpen fullname: Mimpen, Iris organization: University of Montreal Research Center (CRCHUM), Montreal, Quebec, Canada – sequence: 7 givenname: Safae surname: Terrisse fullname: Terrisse, Safae organization: Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France – sequence: 8 givenname: Lisa orcidid: 0000-0003-0527-2964 surname: Derosa fullname: Derosa, Lisa organization: Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France – sequence: 9 givenname: Laurence surname: Zitvogel fullname: Zitvogel, Laurence organization: Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France – sequence: 10 givenname: Bertrand surname: Routy fullname: Routy, Bertrand email: yokuma@ncc.go.jp, bertrand.routy@umontreal.ca organization: Division of Medicine, Department of Hemato-Oncology, University of Montreal Healthcare Center, Montreal, Quebec, Canada – sequence: 11 givenname: Yusuke orcidid: 0000-0001-5743-0149 surname: Okuma fullname: Okuma, Yusuke email: yokuma@ncc.go.jp, bertrand.routy@umontreal.ca organization: Department of Thoracic Oncology, National Cancer Center Hospital, Chuo City, Tokyo, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32847937$$D View this record in MEDLINE/PubMed |
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| Title | The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non-Small Cell Lung Cancer |
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