Cross-reactivity between tumor MHC class I–restricted antigens and an enterococcal bacteriophage

Aurélie Fluckiger, Romain Daillère, Mohamed Sassi, Barbara Susanne Sixt, Peng Liu, Friedemann Loos, Corentin Richard, Catherine Rabu, Maryam Tidjani Alou, Anne Gaëlle Goubet, Fabien Lemaitre, Gladys Ferrere, Lisa Derosa, Connie P.M. Duong, Meriem Messaoudene, Andréanne Gagné, Philippe Joubert, Luisa de Sordi, Laurent Debarbieux, Sylvain SimonClara Maria Scarlata, Maha Ayyoub, Belinda Palermo, Francesco Facciolo, Romain Boidot, Richard Wheeler, Ivo Gomperts Boneca, Zsofia Sztupinszki, Krisztian Papp, Istvan Csabai, Edoardo Pasolli, Nicola Segata, Carlos Lopez-Otin, Zoltan Szallasi, Fabrice Andre, Valerio Iebba, Valentin Quiniou, David Klatzmann, Jacques Boukhalil, Saber Khelaifia, Didier Raoult, Laurence Albiges, Bernard Escudier, Alexander Eggermont, Fathia Mami-Chouaib, Paola Nistico, François Ghiringhelli, Bertrand Routy, Nathalie Labarrière, Vincent Cattoir, Guido Kroemer, Laurence Zitvogel

Research output: Contribution to journalArticlepeer-review

Abstract

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I–binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae. Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2Kb–restricted CD8+ T lymphocyte response upon immunotherapy with cyclophosphamide or anti–PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice. In renal and lung cancer patients, the presence of the enterococcal prophage in stools and expression of a TMP–cross-reactive antigen by tumors correlated with long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing naturally processed cancer antigens that are cross-reactive with microbial peptides were detected.

Original languageEnglish
Pages (from-to)936-942
Number of pages7
JournalScience
Volume369
Issue number6506
DOIs
Publication statusPublished - Aug 21 2020

ASJC Scopus subject areas

  • General

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