Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage
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Peng Liu
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Corentin Richard
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Catherine Rabu
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Anne-Gaëlle Goubet
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Gladys Ferrere
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Lisa Derosa
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Connie Duong
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Laurent Debarbieux
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Clara-Maria Scarlata
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Maha Ayyoub
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Richard Wheeler
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Ivo Gomperts Boneca
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Nicola Segata
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Zoltan Szallasi
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Valerio Iebba
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Valentin Quiniou
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David Klatzmann
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Saber Khelaifia
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Didier Raoult
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François Ghiringhelli
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Bertrand Routy
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Nathalie Labarrière
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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.
Origin : Files produced by the author(s)
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