August 21, 2020
Cross-reactivity between tumor MHC class I–restricted antigens and an enterococcal bacteriophage
Science - 2020
Abstract
Authors: 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 Simon, Clara-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.
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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.
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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.
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