Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses

Nicolas Vallet; Maud Salmona; Jeanne Malet-Villemagne; Maxime Bredel; Louise Bondeelle; Simon Tournier; Séverine Mercier-Delarue; Stéphane Cassonnet; Brian Ingram; Régis Peffault de Latour; Anne Bergeron; Gérard Socié; Jérome Le Goff; Patricia Lepage; David Michonneau

doi:10.1016/j.chom.2023.06.009

Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses

Cell Host Microbe. 2023 Aug 9;31(8):1386-1403.e6. doi: 10.1016/j.chom.2023.06.009. Epub 2023 Jul 17.

Authors

Affiliations

¹ Université de Paris Cité, INSERM U976, 75010 Paris, France.
² Université de Paris Cité, INSERM U976, 75010 Paris, France; Virology Department, AP-HP, Saint-Louis Hospital, 75010 Paris, France.
³ Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
⁴ Pneumology Unit, AP-HP, Saint-Louis Hospital, 75010 Paris, France.
⁵ Core Facilities, Saint-Louis Research Institute, Université de Paris Cité, UAR 2030/US 53, 75010 Paris, France.
⁶ Virology Department, AP-HP, Saint-Louis Hospital, 75010 Paris, France.
⁷ Service de Biostatistique et Information Médicale, AP-HP, Saint-Louis Hospital, 75010 Paris, France.
⁸ Metabolon, Inc., Morrisville, NC 27560, USA.
⁹ Hematology Transplantation, AP-HP, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75010 Paris, France; Cryostem Consortium, 13382 Marseille, France.
¹⁰ Pneumology Department, Geneva University Hospitals, 1205 Geneva, Switzerland.
¹¹ Université de Paris Cité, INSERM U976, 75010 Paris, France; Hematology Transplantation, AP-HP, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75010 Paris, France.
¹² Université de Paris Cité, INSERM U976, 75010 Paris, France; Hematology Transplantation, AP-HP, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75010 Paris, France. Electronic address: [email protected].

PMID: 37463582
DOI: 10.1016/j.chom.2023.06.009

Abstract

Early administration of azithromycin after allogeneic hematopoietic stem cell transplantation was shown to increase the relapse of hematological malignancies. To determine the impact of azithromycin on the post-transplant gut ecosystem and its influence on relapse, we characterized overtime gut bacteriome, virome, and metabolome of 55 patients treated with azithromycin or a placebo. We describe four enterotypes and the network of associated bacteriophage species and metabolic pathways. One enterotype associates with sustained remission. One taxon from Bacteroides specifically associates with relapse, while two from Bacteroides and Prevotella correlate with complete remission. These taxa are associated with lipid, pentose, and branched-chain amino acid metabolic pathways and several bacteriophage species. Enterotypes and taxa associate with exhausted T cells and the functional status of circulating immune cells. These results illustrate how an antibiotic influences a complex network of gut bacteria, viruses, and metabolites and may promote cancer relapse through modifications of immune cells.

Keywords: allogeneic hematopoietic stem cell transplantation; antibiotics; antitumor immune responses; azithromycin; cancer; gut virome; hematological relapse; metabolomic; microbiome.

Publication types

Randomized Controlled Trial

MeSH terms

Azithromycin*
Ecosystem
Hematologic Neoplasms*
Humans
Neoplasm Recurrence, Local
T-Lymphocytes

Substances

Azithromycin