Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer
Por:
F. ZHANG, M. FERRERO, N. DONG, G. D'AURIA, M. REYES-PRIETO, A. HERREROS-POMARES, S. CALABUIG-FARINAS, E. DURENDEZ, F. APARISI, A. BLASCO, C. GARCIA, C. CAMPS, E. JANTUS-LEWINTRE and R. SIRERA
Publicada:
1 jun 2021
Resumen:
Simple Summary
The immune checkpoint blockade (ICB), and concretely the blockade of the PD1/PDL1 axis, has opened up a new standard of treatment for non-small cell lung cancer (NSCLC). However, despite substantial advances in clinical care, many patients still remain refractory to these therapies. Biomarkers such as PD-L1 expression and tumor mutational burden have been associated with ICB efficacy, but the mechanisms underlying variable responses are not yet fully understood. Recently, the differential composition of the gut microbiota was studied as one of the variables accounting for interpatient heterogeneity in ICB responses. To better understand the potential role of the gut microbiota as a biomarker for immunotherapy, we prospectively collected microbiota samples from advanced NSCLC patients starting treatment with ICB. The identification of certain bacteria genera associated with clinical outcomes to ICB in NSCLC may provide novel potential predictive and prognostic biomarkers useful for patient selection and therapy optimization.
Background: The human gut harbors around 10(13)-10(14) microorganisms, collectively referred to as gut microbiota. Recent studies have found that the gut microbiota may have an impact on the interaction between immune regulation and anti-cancer immunotherapies. Methods: In order to characterize the diversity and composition of commensal microbiota and its relationship with response to immune checkpoint blockade (ICB), 16S ribosomal DNA (rDNA) sequencing was performed on 69 stool samples from advanced non-small cell lung cancer (NSCLC) patients prior to treatment with ICB. Results: The use of antibiotics and ICB-related skin toxicity were significantly associated with reduced gut microbiota diversity. However, antibiotics (ATB) usage was not related to low ICB efficacy. Phascolarctobacterium was enriched in patients with clinical benefit and correlated with prolonged progression-free survival, whereas Dialister was more represented in patients with progressive disease, and its higher relative abundance was associated with reduced progression-free survival and overall survival, with independent prognostic value in multivariate analysis. Conclusions: Our results corroborate the relation between the baseline gut microbiota composition and ICB clinical outcomes in advanced NSCLC patients, and provide novel potential predictive and prognostic biomarkers for immunotherapy in NSCLC.
Filiaciones:
F. ZHANG:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
M. FERRERO:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
N. DONG:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
G. D'AURIA:
FISABIO, Fundacio Foment Invest Sanitaria & Biomed Comunit, Sequencing & Bioinformat Serv, Valencia 46020, Spain
CIBERESP, Ctr Invest Biomed Red Epidemiol & Salud Publ, Madrid 28029, Spain
M. REYES-PRIETO:
FISABIO, Fundacio Foment Invest Sanitaria & Biomed Comunit, Sequencing & Bioinformat Serv, Valencia 46020, Spain
Univ Valencia, Inst Integrat Syst Biol, Evolutionary Genet, Valencia 46980, Spain
Spanish Res Council, Valencia 46980, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
Univ Valencia, Dept Pathol, Valencia 46010, Spain
E. DURENDEZ:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
F. APARISI:
Hosp Gen Requena, Dept Med Oncol, Valencia 46340, Spain
A. BLASCO:
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
C. GARCIA:
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
Univ Valencia, Dept Med, Valencia 46010, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia 46022, Spain
R. SIRERA:
Hosp Gen Univ Valencia, Fdn Invest, Ctr Invest Principe Felipe, Unidad Mixta TRIAL, Valencia 46014, Spain
CIBERONC, Ctr Invest Biomed Red Canc, Madrid 28029, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia 46022, Spain
Gold, Green Published
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