In:
Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-4-21)
Abstract:
Programmed death 1 (PD-1) and the ligand of PD-1 (PD-L1) are central targets for immune-checkpoint therapy (ICT) blocking immune evasion-related pathways elicited by tumor cells. A number of PD-1 inhibitors have been developed, but the efficacy of these inhibitors varies considerably and is typically below 50%. The efficacy of ICT has been shown to be dependent on the gut microbiota, and experiments using mouse models have even demonstrated that modulation of the gut microbiota may improve efficacy of ICT. Methods We followed a Han Chinese cohort of 85 advanced non-small cell lung cancer (NSCLC) patients, who received anti-PD-1 antibodies. Tumor biopsies were collected before treatment initiation for whole exon sequencing and variant detection. Fecal samples collected biweekly during the period of anti-PD-1 antibody administration were used for metagenomic sequencing. We established gut microbiome abundance profiles for identification of significant associations between specific microbial taxa, potential functionality, and treatment responses. A prediction model based on random forest was trained using selected markers discriminating between the different response groups. Results NSCLC patients treated with antibiotics exhibited the shortest survival time. Low level of tumor-mutation burden and high expression level of HLA-E significantly reduced progression-free survival. We identified metagenomic species and functional pathways that differed in abundance in relation to responses to ICT. Data on differential enrichment of taxa and predicted microbial functions in NSCLC patients responding or non-responding to ICT allowed the establishment of random forest algorithm-adopted models robustly predicting the probability of whether or not a given patient would benefit from ICT. Conclusions Overall, our results identified links between gut microbial composition and immunotherapy efficacy in Chinese NSCLC patients indicating the potential for such analyses to predict outcome prior to ICT.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2022.837525
DOI:
10.3389/fonc.2022.837525.s001
DOI:
10.3389/fonc.2022.837525.s002
DOI:
10.3389/fonc.2022.837525.s003
DOI:
10.3389/fonc.2022.837525.s004
DOI:
10.3389/fonc.2022.837525.s005
DOI:
10.3389/fonc.2022.837525.s006
DOI:
10.3389/fonc.2022.837525.s007
DOI:
10.3389/fonc.2022.837525.s008
DOI:
10.3389/fonc.2022.837525.s009
DOI:
10.3389/fonc.2022.837525.s010
DOI:
10.3389/fonc.2022.837525.s011
DOI:
10.3389/fonc.2022.837525.s012
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2649216-7
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