Search

Your search keyword '"Mevyn Nizard"' showing total 5 results
Start Over Author "Mevyn Nizard" Topic medicine.anatomical_structure
5 results on '"Mevyn Nizard"'

1. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors

Author

Elie Marcheteau, Mevyn Nizard, Hideo Yagita, Eric Tartour, Pierre Combe, Corinne Tanchot, Sabrina Latreche, Thibault Voron, Nadine Benhamouda, Julien Taieb, Franck Zinzindohoué, Magali Terme, Anne-Laure Pointet, Sonia Bergaya, Christian Stockmann, Orianne Colussi, Anne Berger, and Simon Pernot

Subjects
Vascular Endothelial Growth Factor A, T cell, Programmed Cell Death 1 Receptor, Immunology, CD8-Positive T-Lymphocytes, Biology, Inhibitory postsynaptic potential, Mice, Lymphocytes, Tumor-Infiltrating, Immune system, Neoplasms, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, CTLA-4 Antigen, Loss function, Tumor microenvironment, Gene Expression Profiling, Brief Definitive Report, food and beverages, Cell biology, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Vascular endothelial growth factor A, Receptors, Vascular Endothelial Growth Factor, medicine.anatomical_structure, Female, CD8, Protein Binding, Signal Transduction
Abstract

VEGF-A production in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved with CD8+ T cell exhaustion, which can be reversed with anti-VEGF/VEGFR treatment., Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8+ T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A–VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.

Published
2015
Full Text
View/download PDF

2. Mucosal vaccines: Novel strategies and applications for the control of pathogens and tumors at mucosal sites

Author

Thi Thuy Hien Tran, Eric Tartour, Mariana de Oliveira Diniz, Helene Roussel, Luis Cs Ferreira, Mevyn Nizard, and Cécile Badoual

Subjects
Pharmacology, Vaccines, Mucosal Immune Responses, T cell, Immunology, SISTEMA IMUNE, Review, Biology, biochemical phenomena, metabolism, and nutrition, medicine.anatomical_structure, Immune system, Immunization, medicine, Immunology and Allergy, bacteria, Administration, Mucosal, Animals, Humans, Immunity, Mucosal
Abstract

The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.

Published
2014

3. Comprehensive analysis of current approaches to inhibit regulatory T cells in cancer

Author

Françoise Quintin-Colonna, Claire Banissi, Hélène Péré, Olivier Adotevi, Magali Terme, Julien Taieb, Nathalie Merillon, Mevyn Nizard, Jagadeesh Bayry, Ve´ronique Quillien, Ste´phane Oudard, Eric Tartour, Alain Carpentier, Wolf H. Fridman, Cécile Badoual, Corinne Tanchot, Elie Marcheteau, Federico Sandoval, Laurence Zitvogel, Guido Kroemer, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatogastro-entérologie et d'oncologie digestive, 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), Service d'anatomo-pathologie [CHU HEGP], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Service de Biologie, CRLCC Eugène Marquis (CRLCC), École nationale vétérinaire d'Alfort (ENVA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Pôle de biologie, Laboratoire d'Immunologie Cellulaire et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), School of Medicine, Université Paris-Sud - Paris 11 (UP11), Service d'oncologie médicale [CHU HEGP], Jonchère, Laurent, Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Structures et Marché Agricoles, Ressources et Territoires (SMART), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), CRLCC Eugène Marquis ( CRLCC ), École nationale vétérinaire d'Alfort ( ENVA ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR58-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)

Subjects
Chemokine, regulatory T cell, Regulatory T cell, T cell, Immunology, Population, chemical and pharmacologic phenomena, Review, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, 0302 clinical medicine, medicine, antiangiogenic molecule, Immunology and Allergy, IL-2 receptor, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, education, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, business.industry, chemokine, FOXP3, hemic and immune systems, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, biology.protein, CCR4, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Tyrosine kinase
Abstract

International audience; CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) have emerged as a dominant T cell population inhibiting anti-tumor effector T cells. Initial strategies used for Treg-depletion (cyclophosphamide, anti-CD25 mAb ...) also targeted activated T cells, as they share many phenotypic markers. Current, ameliorated approaches to inhibit Treg aim to either block their function or their migration to lymph nodes and the tumor microenvironment. Various drugs originally developed for other therapeutic indications (anti-angiogenic molecules, tyrosine kinase inhibitors, etc) have recently been discovered to inhibit Treg. These approaches are expected to be rapidly translated to clinical applications for therapeutic use in combination with immunomodulators.

Published
2012
Full Text
View/download PDF

4. Abstract 2830: Mucosal imprinting of vaccine induced-CD8+T cells is crucial to inhibit mucosal tumors

Author

Wolf H. Fridman, Françoise Quintin-Colonna, Michel-Francis Bureau, Estelle Dransart, Federico Sandoval, Magali Terme, Alain Gey, Eric Tartour, Tzyy Choou Wu, Mevyn Nizard, Ludger Johannes, Cécile Badoual, Gwenhael Autret, Elie Marcheteau, and Olivier Clément

Subjects
Cancer Research, business.industry, Spleen, Dendritic cell, medicine.disease, Vaccination, medicine.anatomical_structure, Immune system, Oncology, Immunology, Medicine, Cytotoxic T cell, Cancer vaccine, business, Lung cancer, CD8
Abstract

Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. The utility of preferentially inducing an anti-tumor immune response in the mucosal anatomic site of tumors has never been addressed. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. For this purpose, we set up original orthotopic models of head and neck and lung cancers monitored by magnetic resonance imaging or luciferase based in vivo optical imaging and vaccine based on a non replicative delivery system, the B subunit of Shiga toxin (STxB) as mucosal vector which has previously been shown to target antigen to dendritic cells. We showed that the growth of orthotopic head and neck or lung cancers expressing the E7 protein from HPV16 was only inhibited, when a cancer vaccine was delivered by the intranasal (i.n) mucosal and not the intramuscular (i.m) route. This anti-tumor effect was dependent on mucosal CD8+T cells as : i) Only a vaccine composed of STxB coupled to an E7 derived polypeptide (STxB-E7), but not the free E7 polypeptide elicited mucosal CD8+T cells. This mucosal induction of anti-E7 CD8+T cells, but not the systemic (spleen) specific anti-E7 CD8+T cells correlated with mucosal tumor protection. ii) A greater mucosal tumor infiltration of CD8+T cells was detected 7 days after tumor graft in mice that had been previously intranasally immunized with STxB-E7, than in mice vaccinated by the i.m. route. iii) CD8+T cell-depleted mice vaccinated with STxB-E7 by the i.n. route died before 20 days, whereas mice survived more than 6 months without CD8 depletion. As control, both routes of vaccine administration controlled the growth of subcutaneous tumors and elicited anti-E7 specific CD8+T cells in the spleen. To explain this finding, we demonstrated that only i.n. 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, only dendritic cell from lung parenchyma, but not from spleen induced the expression of CD49a on co-cultured specific CD8+T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a at higher levels than TIL from non mucosal tumors, supporting 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 controlling their trafficking with a direct application on the efficacy of cancer vaccine to control mucosal tumors. Citation Format: Federico Sandoval, Mevyn Nizard, Magali Terme, Cecile Badoual, Michel-Francis Bureau, Olivier Clement, Elie Marcheteau, Alain Gey, Estelle Dransart, Françoise Quintin-Colonna, Gwenhael Autret, Tzyy-Choou Wu, Wolf H. Fridman, Ludger Johannes, Eric Tartour. Mucosal imprinting of vaccine induced-CD8+T cells is crucial to inhibit mucosal tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2830. doi:10.1158/1538-7445.AM2013-2830

Published
2013
Full Text
View/download PDF

5. Abstract 5388: Local mucosal CD8+T cell response is required to inhibit the growth of orthotopic head and neck and lung cancers

Author

Ludovic Freyburger, Magali Terme, Nathalie Merillon, Estelle Dransart, Guillaume Fraisse, Françoise Quintin-Colonna, Eric Tartour, Federico Sandoval, Ludger Johannes, Olivier Clément, Cécile Badoual, Elie Marcheteau, Tzyy Choou Wu, Alain Gey, Wolf H. Fridman, Michel Bureau, and Mevyn Nizard

Subjects
Cancer Research, business.industry, T cell, Tumor antigen, Immune system, medicine.anatomical_structure, Oncology, Antigen, Immunology, Medicine, Cytotoxic T cell, Cancer vaccine, business, CD8, Tumor Graft
Abstract

Tumors may be located at mucosal or non-mucosal sites. However, the clinical benefit of preferentially inducing an anti-tumor immune response in the anatomic site of tumors has never been addressed. We set up orthotopic models of head and neck and lung cancers to compare the systemic and local anti-tumor immune response after administration of a cancer vaccine by mucosal and systemic routes. We also selected a non replicative delivery system, the B subunit of Shiga toxin (STxB), as a mucosal vector able to target dendritic cells. We show that intranasal immunization of mice with STxB based vaccine is the best route to elicit polyfunctional specific CD8+T cells in cervical and mediastinal lymph node than the use of non vectorized antigen or the intramuscular route. In line with these results, nasal mucosal administration of a model tumor antigen (E7 polypeptide from HPV 16) targeted to dendritic cells by STxB is more efficient to inhibit the growth of established orthotopic head and neck and lung cancers expressing the E7 antigen, than the administration of non vectorized antigen or the use of intramuscular route. A higher infiltration of CD8+T cells was detected 7 days after tumor graft, when mice were previously intranasally immunized with STxB-E7, than in mice vaccinated by the intramuscular route. Specific anti-E7 CD8+T cell tumor infiltration, was only observed after nasal immunization. Indeed, depletion of CD8+T cells inhibited the clinical efficiency of tumor vaccine demonstrating their role in tumor protection. In contrast, both routes completely controlled the growth of a subcutaneously E7 expressing tumor, which correlated with a similar induction of anti-E7 CD8+T cells in the spleen. Analysis of Integrin and chemokine receptor expression on tetramere positive cells showed that intranasal immunization induced higher levels of CD103 on T cells in bronchoalveolar lavage than intramuscular immunization with the same vaccine. This study emphasizes the need to elicit a potent anti-tumor response at the anatomic site of tumor and not just in the systemic compartment to induce tumor regression. This was achieved by i) administration of the vaccine by the intranasal route which was efficient in inducing CD8+T cells response at both locoregional and systemic sites allowing the control of both mucosal and non mucosal tumors. ii) The targeting of antigen to dendritic cells by STxB. This study is relevant to humans, as 30% of head and neck cancers express HPV16. Our results support the development of STxB-E7 vaccine administered by the i.n. route for the treatment of these HPV associated head and neck cancers. More generally, this study provides direct evidence for the compartmentalization of tumor immunity, a critical finding for the design of better cancer vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5388. doi:1538-7445.AM2012-5388

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results