Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: An ancillary study of the SHIVA clinical trial.
Ancillary study
Immunity
Metastases
Microbiota
Targeted sequencing
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
29
10
2022
revised:
14
01
2023
accepted:
25
01
2023
pubmed:
4
3
2023
medline:
21
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites. Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed. We performed bacterial 16S rRNA gene sequencing on these samples to characterise the intratumoral microbiome. We assessed the association between microbiome composition, clinicopathological characteristics, and outcomes. Microbial richness (Chao1 index), evenness (Shannon index) and beta-diversity (Bray Curtis distance) were associated with biopsy site (p = 0.0001, p = 0.03 and p < 0.0001, respectively) but not with primary tumour type (p = 0.52, p = 0.54 and p = 0.82, respectively). Furthermore, microbial richness was inversely associated with tumour-infiltrating lymphocytes (TILs, p = 0.02), and PD-L1 expression on immune cells (p = 0.03), or assessed by Tumor Proportion Score (TPS, p = 0.02) or Combined Positive Score (CPS, p = 0.04). Beta-diversity was also associated with these parameters (p < 0.05). Patients with lower intratumoral microbiome richness had shorter overall survival (p = 0.03) and progression-free survival (p = 0.02) in multivariate analysis. Biopsy site, rather than primary tumour type, was strongly associated with microbiome diversity. Immune histopathological parameters such as PD-L1 expression and TILs were significantly associated with alpha and beta-diversity supporting the cancer-microbiome-immune axis hypothesis.
Sections du résumé
BACKGROUND
Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites.
METHODS
Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed. We performed bacterial 16S rRNA gene sequencing on these samples to characterise the intratumoral microbiome. We assessed the association between microbiome composition, clinicopathological characteristics, and outcomes.
RESULTS
Microbial richness (Chao1 index), evenness (Shannon index) and beta-diversity (Bray Curtis distance) were associated with biopsy site (p = 0.0001, p = 0.03 and p < 0.0001, respectively) but not with primary tumour type (p = 0.52, p = 0.54 and p = 0.82, respectively). Furthermore, microbial richness was inversely associated with tumour-infiltrating lymphocytes (TILs, p = 0.02), and PD-L1 expression on immune cells (p = 0.03), or assessed by Tumor Proportion Score (TPS, p = 0.02) or Combined Positive Score (CPS, p = 0.04). Beta-diversity was also associated with these parameters (p < 0.05). Patients with lower intratumoral microbiome richness had shorter overall survival (p = 0.03) and progression-free survival (p = 0.02) in multivariate analysis.
CONCLUSION
Biopsy site, rather than primary tumour type, was strongly associated with microbiome diversity. Immune histopathological parameters such as PD-L1 expression and TILs were significantly associated with alpha and beta-diversity supporting the cancer-microbiome-immune axis hypothesis.
Identifiants
pubmed: 36868056
pii: S0959-8049(23)00048-5
doi: 10.1016/j.ejca.2023.01.024
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-161Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.