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Article Dans Une Revue European Journal of Cancer Année : 2023

Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: An ancillary study of the SHIVA clinical trial

Marc Hilmi
Maud Kamal
  • Fonction : Auteur
Sophie Vacher
Célia Dupain
  • Fonction : Auteur
Sabrina Ibadioune
  • Fonction : Auteur
Maral Halladjian
Marie Paule Sablin
  • Fonction : Auteur
Grégoire Marret
  • Fonction : Auteur
Zahra Castel Ajgal
Michèle Nijnikoff
  • Fonction : Auteur
Anne Salomon
Zakhia El Beaino
Nicolas Servant
Sylvain Dureau
  • Fonction : Auteur
Harry Sokol
  • Fonction : Auteur
Christophe Le Tourneau
Ivan Bieche
Cindy Neuzillet
  • Fonction : Auteur

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.

Dates et versions

hal-04094778 , version 1 (11-05-2023)

Identifiants

Citer

Marc Hilmi, Maud Kamal, Sophie Vacher, Célia Dupain, Sabrina Ibadioune, et al.. Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: An ancillary study of the SHIVA clinical trial. European Journal of Cancer, 2023, 183, pp.152-161. ⟨10.1016/j.ejca.2023.01.024⟩. ⟨hal-04094778⟩
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