title: Phenotype of NK-Like CD8(+) T Cells with Innate Features in Humans and Their Relevance in Cancer Diseases.
abstract: Unconventional T cells are defined by their capacity to respond to signals other than the well-known complex of peptides and major histocompatibility complex proteins. Among the burgeoning family of unconventional T cells, innate-like CD8(+) T cells in the mouse were discovered in the early 2000s. This subset of CD8(+) T cells bears a memory phenotype without having encountered a foreign antigen and can respond to innate-like IL-12 + IL-18 stimulation. Although the concept of innate memory CD8(+) T cells is now well established in mice, whether an equivalent memory NK-like T-cell population exists in humans remains under debate. We recently reported that CD8(+) T cells responding to innate-like IL-12 + IL-18 stimulation and co-expressing the transcription factor Eomesodermin (Eomes) and KIR/NKG2A membrane receptors with a memory/EMRA phenotype may represent a new, functionally distinct innate T cell subset in humans. In this review, after a summary on the known innate CD8(+) T-cell features in the mouse, we propose Eomes together with KIR/NKG2A and CD49d as a signature to standardize the identification of this innate CD8(+) T-cell subset in humans. Next, we discuss IL-4 and IL-15 involvement in the generation of innate CD8(+) T cells and particularly its possible dependency on the promyelocytic leukemia zinc-finger factor expressing iNKT cells, an innate T cell subset well documented for its susceptibility to tumor immune subversion. After that, focusing on cancer diseases, we provide new insights into the potential role of these innate CD8(+) T cells in a physiopathological context in humans. Based on empirical data obtained in cases of chronic myeloid leukemia, a myeloproliferative syndrome controlled by the immune system, and in solid tumors, we observe both the possible contribution of innate CD8(+) T cells to cancer disease control and their susceptibility to tumor immune subversion. Finally, we note that during tumor progression, innate CD8(+) T lymphocytes could be controlled by immune checkpoints. This study significantly contributes to understanding of the role of NK-like CD8(+) T cells and raises the question of the possible involvement of an iNKT/innate CD8(+) T cell axis in cancer.
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Barbarin
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France; Service d'Hématologie et d'Oncologie Biologique, CHU de Poitiers, Poitiers, France; Université de Poitiers, Poitiers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cayssials
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France; Université de Poitiers, Poitiers, France; Service d'Immunologie et Inflammation, CHU de Poitiers, Poitiers, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jacomet
authors.affiliation: Institut Curie, PSL Research University, INSERM U932, Paris, France; SiRIC Translational Immunotherapy Team, Translational Research Department, Research Center, Institut Curie, PSL Research University, Paris, France; Centre d'Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, France.
authors.forename: Nicolas Gonzalo
authors.initials: NG
authors.lastname: Nunez
authors.affiliation: INSERM 1082, Poitiers, France; Université de Poitiers, Poitiers, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Basbous
authors.affiliation: INSERM 1082 , Poitiers , France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Lefèvre
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Abdallah
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Piccirilli
authors.affiliation: INSERM 1082 , Poitiers , France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Morin
authors.affiliation: INSERM U1242, Rennes, France; CHU de Rennes, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lavoue
authors.affiliation: CHU de Rennes, Rennes, France; INSERM U991, Rennes, France; CRB Santé de Rennes, Rennes, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Catros
authors.affiliation: Institut Curie, PSL Research University, INSERM U932, Paris, France; SiRIC Translational Immunotherapy Team, Translational Research Department, Research Center, Institut Curie, PSL Research University, Paris, France; Centre d'Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Piaggio
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France; Université de Poitiers, Poitiers, France.
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.affiliation: INSERM 1082, Poitiers, France; CHU de Poitiers, Poitiers, France; Université de Poitiers, Poitiers, France; Service d'Immunologie et Inflammation, CHU de Poitiers, Poitiers, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gombert
keywords: CD49d; Eomesodermin; NK-like T cells; chronic myeloid leukemia; iNKT cells; innate memory CD8(+) T cells; natural killer receptors; solid cancers