Highlights
- •The composition of microbiota in metastases is tissue-rather than tumor-driven.
- •PD-L1 and tumor-infiltrating lymphocytes are associated with microbiome diversity.
- •This ancillary study supports the cancer-microbiome-immune axis hypothesis.
Abstract
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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global burden of cancers attributable to infections in 2008: a review and synthetic analysis.Lancet Oncol. 2012; 13: 607-615
- Microbiota in tumors: from understanding to application.Adv Sci. 2022; 9e2200470
- The human tumor microbiome is composed of tumor type-specific intracellular bacteria.Science. 2020; 368: 973-980
- Intratumor microbiome in cancer progression: current developments, challenges and future trends.Biomark Res. 2022; 10: 37
- The intratumoral microbiome: characterization methods and functional impact.Cancer Lett. 2021; 522: 63-79
- Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.Science. 2017; 358: 1443-1448
- Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial.Lancet Oncol. 2015; 16: 1324-1334
- Validation of the Royal Marsden Hospital prognostic score in patients treated in the Phase I Clinical Trials Program at the MD Anderson Cancer Center.Cancer. 2012; 118: 1422-1428
- Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by Oncology Healthcare Professionals.Case Rep Oncol. 2019; 12: 728-736
- The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.Ann Oncol. 2015; 26: 259-271
- The journey of tumor-infiltrating lymphocytes as a biomarker in breast cancer: clinical utility in an era of checkpoint inhibition.Ann Oncol. 2021; 32: 1236-1244
- Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study.Lancet. 2019; 394: 1915-1928
- Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer.N Engl J Med. 2016; 375: 1823-1833
- CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.Oncotarget. 2016; 7: 12024-12034
- Deriving accurate microbiota profiles from human samples with low bacterial content through post-sequencing processing of Illumina MiSeq data.Microbiome. 2015; 3: 19
- FastQ Screen: a tool for multi-genome mapping and quality control.F1000Res. 2018; 7: 1338
- Cutadapt removes adapter sequences from high-throughput sequencing reads.EMBnetjournal. 2011; 17 (Next Generation Sequencing Data Analysis)
- DADA2: high-resolution sample inference from Illumina amplicon data.Nat Methods. 2016; 13: 581-583
- Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data.Microbiome. 2018; 6: 226
- phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data.PLoS One. 2013; 8e61217
- Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.Genome Biol. 2014; 15: 550
- Multivariable association discovery in population-scale meta-omics studies.PLoS Comput Biol. 2021; 17e1009442
- New insights into the cancer-microbiome-immune axis: decrypting a decade of discoveries.Front Immunol. 2021; 12622064
- Tumor microbiome diversity and composition influence pancreatic cancer outcomes.Cell. 2019; 178: 795-806.e12
- Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation.Commun Biol. 2021; 4: 237
- PD-L1 and survival in solid tumors: a meta-analysis.PLoS One. 2015; 10e0131403
- Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.Respir Res. 2021; 22: 322
Article info
Publication history
Published online: February 07, 2023
Accepted:
January 25,
2023
Received in revised form:
January 14,
2023
Received:
October 29,
2022
Footnotes
☆Financial support: This work was supported in part by the Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, Paris, France and the Department of Drug Development and Innovation of Institut Curie (D3i). The SHIVA01 trial was supported by grant ANR-10-EQPX-03 from the Agence Nationale de le Recherche (Investissements d’avenir) and Site de Recherche Intégré contre le Cancer (SiRIC).
Identification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
