Mucosal Imprinting of Vaccine-Induced CD8(+) T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors
2013
Sandoval, Federico | Terme, Magali | Nizard, Mevyn | Badoual, Cecile | Bureau, Michel-Francis | Freyburger, Ludovic | Clément, Olivier | Marcheteau, Elie | Gey, Alain | Fraisse, Guillaume | Bouguin, Cecilia | Merillon, Nathalie | Dransart, Estelle | Tran, Thi | Quintin-Colonna, Francoise | Autret, Gwennhael | Thiébaud, Marine | Suleman, Muhammed | Riffault, Sabine | Wu, Tzyy-Choou | Launay, Odile | Danel, Claire | Taieb, Julien | Richardson, Jennifer | Zitvogel, Laurence | Fridman, Wolf H. | Johannes, Ludger | Tartour, Eric | Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970) ; Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Paris Descartes - Paris 5 (UPD5) | AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO) | Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022) ; Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | École nationale vétérinaire d'Alfort (ENVA) | Institut National de la Santé et de la Recherche Médicale (INSERM) | AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Institut Curie [Paris] | Biologie Cellulaire et Cancer ; Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) | Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Institut National de la Recherche Agronomique (INRA) | Johns Hopkins Medicine ; Partenaires INRAE | AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Université Paris-Sud - Paris 11 (UP11) | Universite Paris Descartes; Ligue contre le Cancer; Agence Nationale de la Recherche; Association pour la Recherche contre le Cancer; Canceropole and Region Ile de France; Institut National du Cancer; Labex Immuno-Oncology | ANR-10-LABX-0015,ImmunoOnco,Immuno-Oncology(2010)
International audience
Show more [+] Less [-]English. Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8(+) T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8(+) T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8(+) T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8(+) T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8(+) T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors.
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