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Immunosurveillance du cancer et ciblage thérapeutique
Objectifs
Le système immunitaire protège l’organisme d’un développement tumoral et notre objectif est d’identifier les mécanismes d’immuno surveillance et d’échappement. Un effort majeur de l’équipe vise à déchiffrer les mécanismes de détection immunitaire innée des stades précoces de la transformation maligne dans le cancer du sein et du côlon en utilisant des approches systémiques non biaisées et biologiques, chez l’homme et la souris. L’hypothèse est que la coopération entre cellules dendritiques (DC) et autres cellules du système immunitaire inné (neutrophiles, NK) permet de détecter la transformation cellulaire et initie l’immunité adaptative. Cet axe de recherche poursuivi par les groupes des Dr Nathalie BENDRISS-VERMARE et Dr Marie-Cécile MICHALLET devrait révéler de nouveaux mécanismes d’échappement qui pourraient être ciblés dans les tumeurs établies.
Des projets complémentaires centrés sur l’immunité adaptative incluent : i) le rôle de l’immunité humorale, des lymphocytes B, structures lymphoïdes tertiaires (TLS) et isotypes d’anticorps, dans le groupe du Dr B. DUBOIS ; et ii) les mécanismes d’immunosuppression médiés par les cellules T régulatrices, dans le groupe du Dr C. MENETRIER-CAUX.
Les cibles identifiées seront poursuivies pour le développement de médicaments et de stratégies d’immunothérapie par le biais de partenariats. Ces programmes sont enrichis par des essais cliniques d’immunothérapie suivis au sein du Laboratoire d’Immunothérapie des Cancers de Lyon (LICL, responsable Dr C. CAUX) permettant d’explorer des hypothèses et de valider des cibles chez les patients.
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Christophe CAUX
Chef d’équipe
christophe.caux@lyon.unicancer.frCheney D – 3ème étage
Centre Léon Bérard
Membres de l'équipe
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COUTZAC Clélia
Oncologue médical CLB - Equipe C Caux
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Principaux financements
INSERM
CNRS
Université Claude Bernard Lyon I
Institut National du Cancer (INCa)
Association pour la Recherche sur le Cancer (ARC)
Ligue Nationale contre le Cancer (Comités de l’Ain, de l’Ardèche, de la Drôme, du Puy de Dôme, du Rhône, de Savoie et de Saône et Loire)
Agence Nationale pour la Recherche (ANR)
Région Auvergne Rhône-Alpes
Lyon Biopole
Laboratoire d’Excellence (LabEx) DevWeCan (Grand Emprunt)
Fondation pour la Recherche Médicale (FRM)
Principales collaborations nationales
Institut Gustave Roussy (Villejuif) / Laurence ZITVOGEL
INSERM U851 (Lyon) / Jacqueline MARVEL et Thierry WALZER
Institut de Recherche Thérapeutique IRT UN Unité INSERM 892, Centre de Recherche en Cancérologie Nantes-Angers (Nantes) / Henri VIE
Institut Curie (Paris) / Sebastian AMIGORENA, Vassili SOUMELIS, …
Université Pierre et Marie Curie (Paris) / Benoit SALOMON et Gilles MARODON
INSERM U631 (CIML, Marseille) / Marc DALOD et Bernard MALISSEN
Laboratoire d’Immunologie des Tumeurs, Centre de Recherche en Cancérologie de Marseille (Marseille) / Daniel OLIVE
INRA (Jouy en Josas) / Nicolas BERTHO et Isabelle SWARTZ-CORNIL
Institut de Biologie Structurale (Grenoble) / Franck FIESCHI
Institut de Génétique Moléculaire de Montpellier (Montpellier) / Marc PIECHAZYCK
Société BASF (Lyon) / Valérie ANDRE et Nicolas BECHETOILLE
Groupe Hospitalier Pitié Salpêtrière (Paris) / Dr Jean-Baptiste BACHET
Groupe Hospitalier Universitaire Ambroise Paré (Paris) / Pr Jean-François EMILE
Hôpital de la TIMONE / Dr Sébastien SALAS
Institut Bergonié (Bordeaux) / Pr Jean Michel COINDRE, Dr Isabelle HOSTIEN, Dr Frederic CHIBON
ImmunID Technologies (Grenoble) / N. PASQUAL
Université d’Auvergne/CHU (Clermont Ferrand) / Marc BERGER
INSERM U1035 (Bordeaux) / Jean-Max PASQUET
CNRS 8619-IBBMC (Orsay) / Michel LEPOIVRE
USR3010 – LJC CNRS (Lyon) Equipe Mechano-genetics of the cell / Françoise ARGOUL
Faculté de medicine, U895 (Nice) Cell death differentiation and cancer / Dr Patrick AUBERGER
Principales collaborations internationales
Société ROCHE (Penzberg, Allemagne) Carola RIES
Société GlaxoSmithKline (Brentford, UK/Agnes Goetschel)
Brad NELSON (Victoria British Columbia, Canada)
PHARMAMAR (Carlos GALMARINI, colmenar viejo, espagne)
Publications
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Mdr1-expressing CD4+ t cells with TH1.17 features resist to neoadjuvant chemotherapy and are associated with breast cancer clinical response
Anthony Di Roio, Margaux Hubert, Laurie Besson, Marion Bossennec, Céline Rodriguez,Yenkel Grinberg-Bleyer, Guilhem Lalle, Lyvia Moudombi, Raphael Schneider, Cyril Degletagne, Isabelle Treilleux, Daniel J Campbell, Séverine Metzger, Thomas Duhen, Olivier Trédan, Christophe Caux, Christine Ménétrier-Caux The Journal for ImmunoTherapy of Cancer
TCR-engineered T cell therapy in solid tumors: State of the art and perspectivesBaulu E, Gardet C, Chuvin N, Depil S Science Advances
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Gene signature of circulating platelet-bound neutrophils is associated with poor prognosis in cancer patients
Lecot P, Ardin M, Dussurgey S, Alcazer V, Moudombi L, Hubert M, Swalduz A, Hernandez-Vargas H, Viari A, Caux C, Michallet MC Int J Cancer
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy.Vincent Alcazer, Paola Bonaventura, Laurie Tonon, Emilie Michel, Virginie Mutez, Clémentine Fabres, Nicolas Chuvin, Rasha Boulos, Yann Estornes, Véronique Maguer-Satta, Kevin Geistlich, Alain Viari, Klaus H. Metzeler, Wolfgang Hiddemann, Aarif M. N. Batch, Tobias Herold, Christophe Caux, Stéphane Depil
The effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: Protocol for the ERICA feasibility trial
American Journal of HematologyGouez M, Pérol O, Pérol M, Caux C, Ménétrier-Caux C, Villard M, Walzer T, Delrieu L, Saintigny P, Marijnen P, Pialoux V, Fervers B. BMJ Open
Identification of shared tumor epitopes from endogenous retroviruses inducing high avidity cytotoxic T cells for cancer immunotherapyP. Bonaventura, V. Alcazer, V. Mutez, L. Tonon, J. Martin, N Chuvin, E Michel, R Boulos, Y Estornes, J. Valladeau-Guilemond, A. Viari, C. Caux, S. Depil. Science Advances
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Type 1 conventional dendritic cells and interferons are required for spontaneous CD4+ and CD8+ T-cell protective responses to breast cancer
Mattiuz R, Brousse C, Ambrosini M, Cancel JC, Bessou G, Mussard J, Sanlaville A, Caux C, Bendriss-Vermare N, Valladeau-Guilemond J, Dalod M, Crozat K. Clin Transl Immunology
The cGAS-STING pathway: a new “innate” weapon against cancerBacar H, Michallet MC. Med Sci (Paris)
Early changes in the immune microenvironment of oral potentially malignant disorders reveal an unexpected association of M2 macrophages with oral cancer free survivalBouaoud J, Foy JP, Tortereau A, Michon L, Lavergne V, Gadot N, Boyault S, Valantin J, De Souza G, Zrounba P, Bertolus C, Bendriss-Vermare N, Saintigny P. Oncoimmunology
Recruitment and expansion of Treg cells in the tumor environment – How to target them?Cinier J, Hubert M, Besson L, Di Roio A, Rodriguez C, Lombardi V, Caux C, Ménétrier-Caux C Cancers
Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancerCohen, R., Jonchère, V., De La Fouchardière, C., Ratovomanana, T., Letourneur, Q., Ayadi, M., Armenoult, L., Buisson, A., Sarabi, M., Pellat, A., et al. J Immunother Cancer
4-Substituted-1,2,3-triazolo nucleotide analogues as CD73 inhibitors, their synthesis, in vitro screening, kinetic and in silico studies Immunosurveillance du cancer et ciblage thérapeutiqueGhoteimi R, Braka A, Rodriguez C, Cros-Perrial E, Nguyen VT, Uttaro JP, Mathé C, Chaloin L, Ménétrier-Caux C, Jordheim LJ, Peyrottes S. Bioorganic Chemistry
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Hepatitis B virus exploits C-type lectin receptors to hijack cDC1s, cDC2s and pDCs
Ouaguia L, Dufeu-Duchesne T, Leroy V, Decaens T, Reiser JB, Sosa Cuevas E, Durantel D, Valladeau-Guilemond J, Bendriss-Vermare N, Chaperot L, Aspord C. Clinical & Translational Immunology
BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s reveal distinct pathophysiologic features and impact on clinical outcomes in melanoma patientsSosa Cuevas E, Ouaguia L, Mouret S, Charles J, De Fraipont F, Manches O, Valladeau-Guilemond J, Bendriss-Vermare N, Chaperot L, Aspord C. Clinical & Translational Immunology
Neoadjuvant immune checkpoint inhibitors in cancer, current state of the artO Le Saux, Y Lounici, P Wajda, S Barrin, C Caux, B Dubois, and I Ray-Coquard. Critical Reviews in Oncology/hematology
Viral reactivation in acute leukemia patients receiving allogeneic hematopoietic stem cell transplantation in complete remission: stimulation of the immune systemLoron S, Sobh M, Lina B, Ader F, Renault M, Michallet MC, Labussiere H, Michallet M. Blood
Expression of TAM-R in human immune cells and unique regulatory function of MERTK in IL-10 production by tolerogenic DC. Giroud, S. Renaudineau, L. Gudefin, A. Calcei, T. Menguy, C. Rozan, J. Mizrahi, C. Caux, V. Duong and J. Valladeau-Guilemond Frontiers Immunology
Inflammasome Deletion Promotes Anti-tumor NK Cell Function in an IL-1/IL-18 Independent Way in Murine Invasive Breast CancerGuey B, Bodnar-Wachtel M, Drouillard A, Eberhardt A, Pratviel M, Goutagny N, Bendriss-Vermare N, Puisieux I, Caux C, Walzer T, Petrilli V. Frontiers in Oncology
Compared descriptive analysis of immunologic landscape in soft tissue sarcoma and GISTDufresne A, Lesluyes T, Ménétrier-Caux C, Brahmi M, Darbo E, Toulmonde M, Italiano A, Mir O, Le Cesne A, Le Guellec S, Valentin T, Chevreau C, Bonvalot S, Penel N, Coindre JM, Caux C, Blay JY, Chibon F. OncoImmunology
Durable and controlled depletion of neutrophils in miceBoivin G, Faget J, Ancey PB, Gkasti A, Mussard J, Engblom C, Pfirschke C, Contat C, Pascual J, Vazquez J, Bendriss-Vermare N, Caux C, Vozenin MC, Pittet MJ, Gunzer M, Meylan E. Nature Communications
IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancerHubert M, Gobbini E, Couillault C, Manh TV, Doffin AC, Berthet J, Rodriguez C, Ollion V, Kielbassa J, Sajous C, Treilleux I, Tredan O, Dubois B, Dalod M, Bendriss-Vermare N, Caux C*, Valladeau-Guilemond J*. (*co-last authorship) Science Immunology
Current advances in immunotherapy in ovarian cancerLe Saux O, Dubois B, Stern MH, Terme M, Tartour E, Classe JM, Chopin N, Trédan O, Caux C, Ray-Coquard I. Bull Cancer.
CD163+ TAMs accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytesRamos RN, Rodriguez C, Hubert M, Ardin M, Treilleux I, Ries CH, Lavergne E, Chabaud S, Colombe A, Trédan O, Gomes Guedes H, Laginha F, Richer W, Piaggio E, Barbuto JAM, Caux C*, Ménétrier-Caux C*, and Bendriss-Vermare N*(* co-last authorship) Clinical & Translational Immunology
Repurposing infectious disease vaccines for intratumoral immunotherapyMelero I, Gato M, Shekarian T, Aznar A, Valsesia-Wittmann S, Caux C, Etxeberrria I, Teijeira A, Marabelle A. J Immunother Cancer
Repurposing infectious disease vaccines for intratumoral immunotherapyMelero I, Gato M, Shekarian T, Aznar A, Valsesia-Wittmann S, Caux C, Etxeberrria I, Teijeira A, Marabelle A. J Immunother Cancer .
Le rôle des lymphocytes T régulateurs dans l’activité anti-tumorale des anti-CTLA-4Thierry K & Ménétrier-Caux C. Médecine & Science
Neutrophils and cancer: discovery of a new mechanism of cellular toxicity and therapeutic perspectivesVictoor C. and Dubois B. Med Sci (Paris)
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Hepatitis B Virus-induced modulation of liver macrophage function promotes hepatocyte infection
Faure-Dupuy S, Delphin M, Aillot L, Dimier L, Lebossé F., Fresquet J, Parent R, Matter MS, Rivoire M, Bendriss-Vermare N, Salvetti A, Heide D, Flores L, Klumpp K, Lam A, Zoulim F, Heikenwaelder M, Durantel D, and Lucifora J Journal of Hepatology
Methotrexate restores CD73 expression on Th1.17 in rheumatoid arthritis and psoriatic arthritis patients and may contribute to its anti-inflammatory effect through Ado productionBossennec M, Rodriguez C, Hubert M, Di-Roio A, Machon C, Jérôme Guitton J, Battiston-Montagne P, Couturier M, Marotte H, Caux C, Coury F, Ménétrier-Caux C. Journal of Clinical Medicine
Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockadeShekarian T, Sivado E, Jallas AC, Depil S, Kielbassa J, Janoueix-Lerosey I, Hutter G, Goutagny N, Bergeron C, Viari A, Valsesia-Wittmann S, Caux C, Marabelle A. Sci Transl Med.
Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cellsMastelic-Gavillet B, xNavarro Rodrigo B, Décombaz L, Wang H, Ercolano G, Rita Ahmed1, Elena Lozano L, Ianaro A, Derré L, Valerio M, Tawadros T, Jichlinski P, Tu Nguyen-Ngoc T, Speiser DE, Verdeil G, Gestermann N, Dormond O, Kandalaft L, Coukos G, Jandus C, Ménétrier-Caux C, Caux C, Ho PC, Romero P, Harari A, Vigano S Journal of Immunotherapy of Cancer
Neutrophil heterogeneity in cancer: from biology to therapiesLecot P, Sarabi M, Pereira Abrantes M, Mussard J, Koenderman L, Caux C, Bendriss-Vermare N, Michallet M-C. Frontiers in Immunology.
Human tumor-infiltrating dendritic cells: from in situ visualization to high throughput analysesHubert M, Gobbini E, Bendriss-Vermare N, Caux C, Valladeau-Guilemond J. Cancers
Targeting adenosine in cancer immunotherapy to enhance T-cell functionVigano S, Alatzoglou D, Irving M, Ménétrier Caux C, Caux C, Romero P, Coukos G Frontiers in Immunology
A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune systemBurlion A, Ramos RN, Pukar KC, Sendeyo K, Corneau A, Ménétrier-Caux C, Piaggio E, Olive D, Caux C and Marodon G Oncoimmunology
Lymphopenia in Cancer Patients and its Effects on Response to Immunotherapy: an opportunity for combination with Cytokines?Ménétrier-Caux C, Ray-Coquard I, Blay JY, Caux C Journal for Immunotherapy of Cancer
Immunopathological characterization of ovarian teratomas associated with anti-N-Methyl-D-Aspartate receptor encephalitisChefdeville A, Treilleux I, Mayeur ME, Couillault C, Picard G, Bost C, Mokhtari K, Vasiljevic A, Meyronet A, Rogemond V, Psimaras D, Dubois B, Honnorat J, Desestret V. Acta Neuropathol. Com.
Cold tumors: a therapeutic challenge for immunotherapyBonaventura P, Shekarian T, Alcazer V, Valladeau-Guilermond J, Valsesia-Wittmann S, Amigorena S. et al Frontiers in Immunology
Circulating and hepatic BDCA1+, BDCA2+, and BDCA3+ dendritic cells are subverted in patients with chronic HBV infectionOuaguia L, Leroy V, Dufeu-Duchesne T, Durantel D, Decaens T, Hubert M, Valladeau-Guilemond J, Bendriss-Vermare N, Chaperot L, Aspord C Frontiers in Immunology
Neoepitopes-based vaccines: challenges and perspectivesAlcazer V, Bonaventura P, Tonon L, Wittmann S, Caux C, Depil S Eur J Cancer
CD73 expression in normal and pathological human hepatobiliopancreatic tissues.Sciarra A, Monteiro I, Ménétrier-Caux C, Caux C, Gilbert B, Halkic N, La Rosa S, Romero P, Sempoux C, de Leval L. Cancer Immunol Immunother
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Immunotherapy and targeted therapy, a promising combination to fight cancer
Andrieu N, Bendriss-Vermare N Med Sci
Contribution of B lymphocytes in acquired resistance to targeted therapies in metastatic melanomaFourneaux C, Dubois B. Med Sci
Hepatitis B Virus Blocks the CRE/CREB Complex and Prevents TLR9 Transcription and Function in Human B CellsTout I, Gomes M, Ainouze M, Marotel M, Pecoul T, Durantel D, Vaccarella S, Dubois B, Loustaud-Ratti V, Walzer T, Alain S, Chemin I, Hasan U J Immunol .
MAVS deficiency induces gut dysbiotic microbiota conferring a pro-allergic phenotypePlantamura E, Dzutsev A, Chamaillard M, Djebali S, Moudombi L, Boucinha L, Grau M, Macari C, Bauché D, Dumitrescu O, Rasigade JP, Lippens S, Plateroti M, Kress E, Cesaro A, Bondu C, Lina G, Bentaher-Belaaouaj A, Marie J, Caux C, Trinchieri G, Marvel J, Michallet MC Proc Natl Acad Sci U S A
MDR1 in immunity: friend or foe?Bossennec M, Di Roio A, Caux C, Ménétrier Caux C. ONcoimmunology
Développement des CAR-T dans les tumeurs solidesAlcazer V, Delenda C, Poirot L, Depil S Bull Cancer
Nouvelles approches vaccinales en cancérologie.Depil S, Bonaventura P, Alcazer V, Tonon L. Bull Cancer
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BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
Combes A, Camosseto V, N’Guessan P, Argüello RJ, Mussard J, Caux C, Bendriss-Vermare N, Pierre P & and Gatti E Nature Communications
Cancer immunotherapy via systemic RNA delivery to dendritic cellsRichaud M and Bendriss-Vermare N. Med
Infiltrated B cells promote pancreatic ductal adenocarcinomaSeillet C and Dubois B Med Sci
Neutrophil: an infiltrated agent with new antitumor skillsMazet J, Michallet MC. Med Sci
The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockadeFoy JP, Bertolus C, Michallet MC, Deneuve S, Incitti R, Bendriss-Vermare N, Albaret MA, Ortiz-Cuaran S, Thomas E, Colombe A, Py C, Gadot N, Michot JP, Fayette J, Viari A, Van den Eynde B, Goudot P, Devouassoux-Shisheboran M, Puisieux A, Caux C, Zrounba P, Lantuejoul S, Saintigny P. Ann Oncol
Emerging role of the Unfolded Protein Response in Tumor Immunosurveillance.Vanacker H, Vetters J, Moudombi L, Caux C, Janssens S, Michallet MC. Trends Cancer .
Cross Talk between Inhibitory Immunoreceptor Tyrosine-Based Activation Motif-Signaling and Toll-Like Receptor Pathways in Macrophages and Dendritic CellsHirsch I, Janovec V, Stranska R, Bendriss-Vermare N Front Immunol .