Journal articles

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

Aurélie Fluckiger ^{1, 2} Romain Daillere ^{1, 2} Mohamed Sassi ³ Barbara S Sixt ^{4, 1, 5} Peng Liu ^{1, 5} Friedemann Loos ^{1, 5} Corentin Richard ^{6, 7} Catherine Rabu ⁸ Maryam Tidjani ^{1, 2, 9} Anne-Gaëlle Goubet ^{1, 2} Fabien Lemaitre ¹ Gladys Ferrere ^{1, 2} Lisa Derosa ^{1, 2, 10} Connie Duong ^{1, 2} Meriem Messaoudene ¹¹ Andréanne Gagné ¹¹ Philippe Joubert ¹¹ Luisa de Sordi ^{12, 13} Laurent Debarbieux ¹² Sylvain Simon ⁸ Clara-Maria Scarlata ¹⁴ Maha Ayyoub ¹⁴ Belinda Palermo ¹⁵ Francesco Facciolo ¹⁵ Romain Boidot ¹⁶ Richard Wheeler ¹² Ivo Gomperts Boneca ¹² Zsofia Sztupinszki ¹⁷ Krisztian Papp ¹⁸ Istvan Csabai ¹⁸ Edoardo Pasolli ¹⁹ Nicola Segata ¹⁹ Carlos López-Otín ^{5, 20} Zoltan Szallasi ¹⁷ Fabrice Andre ¹ Valerio Iebba ¹ Valentin Quiniou ²¹ David Klatzmann ²¹ Jacques Boukhalil ⁹ Saber Khelaifia ⁹ Didier Raoult ⁹ Laurence Albiges ¹ Bernard Escudier ¹ Alexander M Eggermont ¹ Fathia Mami-Chouaib ²² Paola Nistico ¹⁵ François Ghiringhelli ¹⁶ Bertrand Routy ²³ Nathalie Labarrière ⁸ Vincent Cattoir ²⁴ Guido E Kroemer ^{1, 25} Laurence Zitvogel ^{1, 2, 10, 25}

1 IGR - Institut Gustave Roussy

2 ITIC - Immunologie anti-tumorale et immunothérapie des cancers

3 BRM - ARN régulateurs bactériens et médecine

4 Umeå University

5 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

6 Centre d'oncologie et de radiothérapie du parc [Dijon]

7 institut GIMI - Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute)

8 CRCINA-ÉQUIPE 3 - Anti-Tumor Immunosurveillance and Immunotherapy

CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers

9 MEPHI - Microbes évolution phylogénie et infections

10 Université Paris-Saclay

11 IUCPQ - Institut Universitaire de Cardiologie et de Pneumologie de Québec

12 Institut Pasteur [Paris]

13 CRSA - Centre de Recherche Saint-Antoine

14 CRCT - Centre de Recherches en Cancérologie de Toulouse

15 National Cancer Institute Regina Elena [Rome, Italy]

16 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]

17 Boston Children's Hospital

18 ELTE - Eötvös Loránd University

19 University of Trento [Trento]

20 Universidad de Oviedo [Oviedo]

21 CIC-BTi - Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière]

22 INTIM - Immunologie intégrative des tumeurs et immunothérapie des cancers

23 CHUM - Centre Hospitalier de l'Université de Montréal

24 CNR - Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes]

25 IUF - Institut Universitaire de France

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Cancer

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https://www.hal.inserm.fr/inserm-02923397
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Submitted on : Thursday, August 27, 2020 - 9:41:46 AM
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