title: The thymus-specific serine protease TSSP/PRSS16 is crucial for the antitumoral role of CD4(+) T cells.
abstract: In cancer, immune cells can play conflicting roles, either protective, by elimination of tumor cells during immune surveillance, or detrimental, by promoting carcinogenesis during inflammation. We report here that the thymus-specific serine protease (TSSP), which is involved in CD4(+) T cell maturation in the thymus, exerts a tumor suppressor activity. Mice genetically deficient for TSSP are highly prone to spontaneous cancer development. The absence of TSSP also increases the rate of induced colitis-associated colorectal (CAC) tumor formation, through exacerbated colon inflammation. Adoptive transfer of T cells in various combinations (CD4(+) and CD8(+) from wild-type and/or knockout mice) into T cell-deficient mice showed that the TSSP-deficient CD4(+) T cell compartment promotes tumor development, associated with high levels of the cytokine IL-17A. Inhibition of IL-17A during CAC tumor formation prevents the increased carcinogenesis and colic immune disequilibrium observed in TSSP-deficient mice. Therefore, our data demonstrate that antitumoral immune surveillance requires thymic TSSP-driven production of CD4(+) T cells contributing to inflammatory balance.
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Brisson
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pouyet
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Prudence
authors.initials: P
authors.lastname: N'guessan
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Noëlla
authors.initials: N
authors.lastname: Lopes
authors.affiliation: CIPHE, Marseille 13009, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Warcollier
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
authors.affiliation: Inserm, U1068, CRCM, Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France. Electronic address: alice.carrier@inserm.fr.
authors.forename: Alice
authors.initials: A
authors.lastname: Carrier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: C472502:PRSS16 protein, human; D012697:Serine Endopeptidases