title: Mucosal imprinting of vaccine-induced CD8⁺ T cells is crucial to inhibit the growth of mucosal tumors.
abstract: 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.
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Federico
authors: F
authors: Sandoval
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Magali
authors: M
authors: Terme
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Mevyn
authors: M
authors: Nizard
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.
authors: Cécile
authors: C
authors: Badoual
authors: Laboratoire de Pharmacologie Chimique et Génétique, UMR 8151 CNRS, 75270 Paris, France.
authors: Michel-Francis
authors: MF
authors: Bureau
authors: Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort 94700, France.
authors: Ludovic
authors: L
authors: Freyburger
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Olivier
authors: O
authors: Clement
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|INSERM, CIC-BT-505, 75014 Paris, France.|AP-HP, Groupe Hospitalier Cochin Broca Hotel-Dieu, Centre d'investigation clinique de vaccinologie Cochin Pasteur, 75014 Paris, France.
authors: Elie
authors: E
authors: Marcheteau
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.
authors: Alain
authors: A
authors: Gey
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Guillaume
authors: G
authors: Fraisse
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Cécilia
authors: C
authors: Bouguin
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Nathalie
authors: N
authors: Merillon
authors: Institut Curie, Centre de Recherche, Traffic, Signaling, and Delivery Laboratory, 75248 Paris Cedex 05, France.|UMR144 CNRS, 75005 Paris, France.
authors: Estelle
authors: E
authors: Dransart
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Thi
authors: T
authors: Tran
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort 94700, France.
authors: Françoise
authors: F
authors: Quintin-Colonna
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
authors: Gwennhael
authors: G
authors: Autret
authors: Institut Curie, Centre de Recherche, Traffic, Signaling, and Delivery Laboratory, 75248 Paris Cedex 05, France.|UMR144 CNRS, 75005 Paris, France.
authors: Marine
authors: M
authors: Thiebaud
authors: UMR 1161 Virologie Inra, Anses, ENVA, 7 avenue du Général de Gaulle, 94704 Maisons-Alfort, France.
authors: Muhammad
authors: M
authors: Suleman
authors: UR892 INRA, 78350 Jouy-en-Josas, France.
authors: Sabine
authors: S
authors: Riffault
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors: Tzyy-Choou
authors: TC
authors: Wu
authors: INSERM, CIC-BT-505, 75014 Paris, France.|AP-HP, Groupe Hospitalier Cochin Broca Hotel-Dieu, Centre d'investigation clinique de vaccinologie Cochin Pasteur, 75014 Paris, France.
authors: Odile
authors: O
authors: Launay
authors: Hopital Bichat, Service d'Anatomie Pathologique, 75018 Paris, France.
authors: Claire
authors: C
authors: Danel
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.
authors: Julien
authors: J
authors: Taieb
authors: UMR 1161 Virologie Inra, Anses, ENVA, 7 avenue du Général de Gaulle, 94704 Maisons-Alfort, France.
authors: Jennifer
authors: J
authors: Richardson
authors: Institut Gustave Roussy, INSERM U1015, CIC-BT507, Faculté Paris Sud Université Paris XI, 94805 Paris, France.
authors: Laurence
authors: L
authors: Zitvogel
authors: Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.
authors: Wolf H
authors: WH
authors: Fridman
authors: Institut Curie, Centre de Recherche, Traffic, Signaling, and Delivery Laboratory, 75248 Paris Cedex 05, France.|UMR144 CNRS, 75005 Paris, France.
authors: Ludger
authors: L
authors: Johannes
authors: INSERM U970 PARCC, 75015 Paris, France.|Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.|Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.|INSERM, CIC-BT-505, 75014 Paris, France.
authors: Eric
authors: E
authors: Tartour
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018928:Immunity, Mucosal; D007273:Injections, Intramuscular; D039001:Integrin alpha Chains / Q000378:metabolism; D039423:Integrin alpha1 / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D022603:Shiga Toxins / Q000008:administration & dosage; D013154:Spleen / Q000276:immunology; D047368:Tumor Burden
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019496:Cancer Vaccines; D039001:Integrin alpha Chains; D039423:Integrin alpha1; D053918:Papillomavirus Vaccines; D022603:Shiga Toxins; C091367:alpha E integrins; C077239:stxB toxin