1. The Hypothesis of the Human iNKT/Innate CD8(+) T-Cell Axis Applied to Cancer: Evidence for a Deficiency in Chronic Myeloid Leukemia
- Author
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Jacomet, Florence, Cayssials, Emilie, Barbarin, Alice, Desmier, Déborah, Basbous, Sara, Lefèvre, Lucie, Levescot, Anaïs, Robin, Aurélie, Piccirilli, Nathalie, Giraud, Christine, Guilhot, François, Roy, Lydia, Herbelin, André, Gombert, Jean-Marc, Barbarin, Alice, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunologie et Inflammation [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie [CHU Poitiers], Agronomie, Institut National de la Recherche Agronomique (INRA)-AgroParisTech, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang Centre-Atlantique, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Clinique d'Hématologie [Créteil], Hôpital Henri Mondor, Communauté Université Paris-Est, Université Paris Descartes - Paris 5 (UPD5), This study was supported by INSERM, CHU de Poitiers, Université de Poitiers, Ligue contre le Cancer du Grand Ouest (Comités départementaux de la Vienne, de la Charente, de la Charente Maritime et des Deux-Sèvres), Association pour la Recherche en Immunologie-Poitou-Charentes (ARIM-PC), Association Laurette Fugain, Ministère de la Recherche, Sport & Collection, and INCa-DGOS 8658 (PRT-K 2015-052)., AgroParisTech-Institut National de la Recherche Agronomique (INRA), INSERM CIC 0802 (INSERM CIC 0802, CHU de Poitiers), Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique de la Réponse aux Infections chez l'Homme, and Institut Pasteur [Paris]
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NK-like CD8(+) T cells ,tyrosine kinase inhibitor ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,chronic myeloid leukemia ,innate CD8(+) T cells ,Immunology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,iNKT cells ,Original Research - Abstract
International audience; We recently identified a new human subset of NK-like [KIR/NKG2A(+)] CD8(+) T cells with a marked/memory phenotype, high Eomesodermin expression, potent antigen-independent cytotoxic activity, and the capacity to generate IFN-γ rapidly after exposure to pro-inflammatory cytokines. These features support the hypothesis that this new member of the innate T cell family in humans, hereafter referred to as innate CD8(+) T cells, has a role in cancer immune surveillance analogous to invariant natural killer T (iNKT) cells. Here, we report the first quantitative and functional analysis of innate CD8(+) T cells in a physiopathological context in humans, namely chronic myeloid leukemia (CML), a well-characterized myeloproliferative disorder. We have chosen CML based on our previous report that IL-4 production by iNKT cells was deficient in CML patients at diagnosis and considering the recent evidence in mice that IL-4 promotes the generation/differentiation of innate CD8(+) T cells. We found that the pool of innate CD8(+) T cells was severely reduced in the blood of CML patients at diagnosis. Moreover, like iNKT and NK cells, innate CD8(+) T cells were functionally impaired, as attested by their loss of antigen-independent cytotoxic activity and IFN-γ production in response to innate-like stimulation with IL-12 + IL-18. Remarkably, as previously reported for IL-4 production by iNKT cells, both quantitative and functional deficiencies of innate CD8(+) T cells were at least partially corrected in patients having achieved complete cytogenetic remission following tyrosine kinase inhibitor therapy. Finally, direct correlation between the functional potential of innate CD8(+) T and iNKT cells was found when considering all healthy donors and CML patients in diagnosis and remission, in accordance with the iNKT cell-dependent generation of innate CD8(+) T cells reported in mice. All in all, our data demonstrate that CML is associated with deficiencies of innate CD8(+) T cells that are restored upon remission, thereby suggesting their possible contribution to disease control. More generally, our study strongly supports the existence of an innate iNKT/innate CD8(+) T-cell axis in humans and reveals its potential contribution to the restoration of tumor immune surveillance.
- Published
- 2017
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