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Randomized Controlled Trial
. 2023 Aug 9;31(8):1386-1403.e6.
doi: 10.1016/j.chom.2023.06.009. Epub 2023 Jul 17.

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

Nicolas Vallet  1 , Maud Salmona  2 , Jeanne Malet-Villemagne  3 , Maxime Bredel  3 , Louise Bondeelle  4 , Simon Tournier  5 , Séverine Mercier-Delarue  6 , Stéphane Cassonnet  7 , Brian Ingram  8 , Régis Peffault de Latour  9 , Anne Bergeron  10 , Gérard Socié  11 , Jérome Le Goff  2 , Patricia Lepage  3 , David Michonneau  12
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Free article
Randomized Controlled Trial

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

Nicolas Vallet et al. Cell Host Microbe. .
Free article

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.

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Conflict of interest statement

Declaration of interests G.S. and R.P.d.L. received a research grant from Alexion Pharmaceuticals. R.P.d.L. received a research grant from Novartis and Pfizer. G.S. received fees from Pharmacyclics LLC, Novartis, Incyte, Alexion, Amgen, and Pfizer. D.M. received fees from Novartis, Incyte, Jazz Pharmaceuticals, and CSL Behring. N.V., J.L.G., P.L., and D.M. have a related patent registered under the reference EP22306850.3.

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