CONTACT

Team Co-Direction

Jean-Yves BLAY
jean-yves.blay
@lyon.unicancer.fr


Christophe CAUX

christophe.caux
@lyon.unicancer.fr


Cheney D - 3rd floor
Centre Léon Bérard
28 rue Laennec
69373 Lyon Cedex 08
France
BLAY Jean-Yves
Co-chef d'équipe
Professeur des Universités - Praticien hospitalier (UCBL - CLB)
jean-yves.blay@lyon.unicancer.fr
CAUX Christophe
Co-chef d'équipe
NEGRIER Sylvie
Professeur des Universités - Praticien hospitalier (UCBL - CLB)
sylvie.negrier@lyon.unicancer.fr
DEZUTTER-DAMBUYANT Colette
DORE Jean-François
BACHELOT Thomas
Praticien hospitalier CLB   
thomas.bachelot@lyon.unicancer.fr
ALBERTI Laurent
DUTOUR Aurélie
MENETRIER-CAUX Christine
PUISIEUX Isabelle
BENDRISS-VERMARE Nathalie
VALLADEAU-GUILEMOND Jenny
CHIGNOL Marie-Christine
DOFFIN-MARVIE Anne-Claire
DUC Adeline
LANCON Agnes
Technicienne CLB    
agnes.lancon@lyon.unicancer.fr
POUJOL Dominique
Technicienne CLB    
dominique.poujol@lyon.unicancer.fr
VERRONESE Estelle
Technicienne CLB    
estelle.verronese@lyon.unicancer.fr
GOURDIN Nicolas
SANLAVILLE Amélien
MICHALLET Marie-Cécile
DUBOIS Bertrand
MOUDOMBI Lyvia
RODRIGUEZ Céline
COUILLAULT Coline
LE LOARER François
GUILLOT Franceline
COX David
MONCHANIN Morgane
MONDERER David
SIMARD François
Voir les objectifs et projets Voir les publications

OBJECTIVES

Our objective is to identify mechanisms involved in immune subversion by cancer cells and to develop therapeutic strategies based on the immunogenicity of tumor cell death and reactivation of immune-surveillance. The tumor models we use are breast and ovarian carcinoma and sarcoma, in which molecular characterization is advanced (leading to the identification of new molecular types), and in which therapy targeted on oncogene showed their first successes. Since 2005, our project has involved two approaches: i) the identification of the immunosuppressive mechanisms induced by tumors, and ii) the characterisation of new mutations driving cancer with the aim to develop cytotoxic therapies specifically targeted on oncogenes combined with an immunotherapy strategy. In clinical terms, it is also fundamental to eradicate cancer stem cells (CaSC), also named Tumor-Initiating Cells, as likely involved in resistance and relapse in cancers. Thus, we will determine some therapeutic combinations able to induce an anti-tumor response with a long term memory in order to prevent relapse and eradicate cancer stem cells. 

COLLABORATION AND FOUNDING

Financial support
INSERM and 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 
Lyon Biopole 
Laboratoire d'Excellence (LabEx) DevWeCan (Grand Emprunt) 
Fondation pour la Recherche Médicale (FRM) 

National Collaborations
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 
> MORE INFORMATION

PUBLICATIONS

2016

  1. Le KS, Thibult ML,Just-Landi S, Pastor S, Gondois-Rey F, Granjeaud S, Broussais F, Bouabdallah R, Colisson R, Caux C, Ménétrier-Caux C, Leroux D, Xerri L and Olive D (2016). Follicular lymphoma B cells generate functional regulatory T cells via ICOS/ICOSL pathway and are inhibited by intratumoral Tregs Cancer Res. in press.
  2. PAN H, Gazarian A, Dubernard JM, Belot A, Michallet MC*, Michallet M* ( *co-last authorship). Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages and Potential Strategies. Frontiers in Immunology in press.Le Luduec JB, Debeer S, Piras F, Andréoni C, Boudet F, Laurent P, Kaiserlian D, Dubois B. (2016) Indradermermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine. Vaccine 34: 914-922.
  3. Moro-Sibilot L, This S, Blanc P, Sanlaville A, Sisirak V, Bardel E, Boschetti G, Bendriss-Vermare N, Defrance T, Dubois B, Kaiserlian D. Plasmacytoid dendritic cells are dispensable for non-infectious intestinal IgA responses in vivo.  Eur J Immunol. 2016 Feb;46(2):354-9.
  4. Duraes FV, Lippens C, Steinbach K, Dubrot J, Brighouse D, Bendriss-Vermare N, Issazadeh-Navikas S, Merkler D, Hugues S. (2015) pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation. J Autoimmun. 2016 Feb;67:8-18.

2015

  1. Verronèse E, Delgado A, Valladeau-Guilemond J, Garin G, Guillemaut S, Tredan O, Ray-Coquard I, Bachelot T, N’Kodia A, Bardin C, Rigal C, Pérol D, Caux C*, Ménétrier-Caux C* ( *co-last authorship) (2015) Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay. OncoImmunology 5(3):e1100791.
  2. Dezutter-Dambuyant C, Durand I, Alberti L, Bendriss-Vermare N, Valladeau-Guilemond J, Duc A, Magron A,  Morel AP, Sisirak V, Rodriguez C, Cox D, Olive D, Caux C. (2015) A novel regulation of PD-1 Ligands on Mesenchymal Stromal Cells through MMP-mediated proteolytic cleavage. OncoImmunology 5(3):e1091146.
  3. Ghirelli C, Reyal F, Jeanmougin M, Zollinger R, Sirven P, Michea P, Caux C, Bendriss-Vermare N, Donnadieu MH, Caly M, Fourchotte V, Vincent-Salomon A, Sigal-Zafrani B, Sastre-Garau X, Soumelis V. (2015). Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes. Cancer Res. 75(14):2775-87.
  4. Trédan O≠, Ménétrier-Caux C≠, Ray-Coquard I≠, Garin G, Cropet C, Verronèse E, Bachelot T, Rebattu P, Heudel PE, Cassier P, Chabaud S, Croughs T, Dupont P, Cadore AC, Clapisson G, Delgado A, Bardin-dit-Courageot, Rigal C, N’Kodia A, Gilles-Afchain L, Morre M, Pérol D, Blay JY*, Caux C* (≠co-first authorship, * co-last authorship).  (2015) ELYPSE-7: A randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients. Ann Oncol. 26(7):1353-62.
  5. Dupuis-Maurin V, Brinza L, Baguet J, Plantamura E, Schicklin S, Chambion S, Macari C, Tomkowiak M, Deniaud E, Leverrier Y, Marvel J*, Michallet MC*. (*co-last authorship) (2015) Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway. Plos One. 10(3):e0118551.
  6. Pan H, Gazarian A, Buff S, Solla F, Gagnieu MC, Leveneur O, Watrelot-Virieux D, Morisset S, Sobh M, Michallet MC, Roger T, Dubernard JM, Michallet M. (2015) Oral cyclosporine A in neonatal swines for transplantation studies. Immunopharmacology and Immunotoxicology. 37(1):19-25.
  7. Mathieu AL, Verronese E, Rice GI,Fouyssac F, Bertrand Y, Picard C, Chansel M, Walter JE, Notarangelo LD,  Butte M, Nadeau KC, Csomos K, Chen DJ, Chen K, Delgado A, Rigal C, Bardin C, Schuetz C, Moshous D, Reumaux H, Plenat F, Phan A, Zabot M, Balme B,Viel S, Bienvenu J, Cochat P, van Der Burg M, Caux C, Kemp H, Rouvet I, Malcus C, Crow YJ,Fabien N, Ménétrier-Caux C, De Villartay JP, Walzer T and Belot A. (2015) PRKDC mutations associated with immunodeficiency, granuloma and AIRE-dependent auto-immunity. J Allergy Clin Immunol. 135(6):1578-88.e5.

2014

  1. Dutour A, Josserand V, Jury D, Guillermet S, Decouvelaere AV, Chotel F, Pointecouteau T, Rizo P, Coll JL, Blay JY. (2014) Targeted imaging of αvβ3 expressing sarcoma tumor cells in vivo in pre-operative setting using near infrared: A potential tool to reduce incomplete surgical resection. Bone. 62:71-8.
  2. Deauvieau F, Ollion V, Doffin AC, Verronese E., Durand I, Ghittoni R, Marvel J, Walzer T, Vie H., Perrot I., Goutagny N., Caux C*. and Valladeau-Guilemond J*. (2014) Human natural killer cells promote tumor cell-derived antigen cross presentation by dendritic cells through cytokine production. Int J Cancer 136(5):1085-94. *co-senior authors
  3. Zannetti C, Parroche P, Panaye M, Roblot G, Gruffat H, Manet E, Debaud AL, Plumas J, Vey N, Caux C, Bendriss-Vermare N, Hasan UA. TLR9 transcriptional regulation in response to double-stranded DNA viruses. J Immunol. 2014 Oct 1;193(7):3398-408.
  4. Balan S, Ollion V, Colletti N, Chelbi R, Montanana-Sanchis F, Liu H, Vu Manh T-P, Sanchez C, Savoret J, Perrot I, Doffin AC, Fossum E, Bechlian D, Chabannon C, Bogen B, Asselin-Paturel C, Shaw M, Soos T, Caux C, Valladeau-Guilemond J*, Dalod M*. (2014) Human XCR1+ DC derived in vitro from CD34+ progenitors closely resemble blood DC including by their adjuvant responsiveness, contrary to monocyte-derived DC. J Immunol. 193(4):1622-35.*co-senior authors

2013

  1. Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, Zhou G, Rajapaksa R, Green MR, Torchia J, Brody J, Luong R, Rosenblum MD, Steinman L, Levitsky HI, Tse V, Levy R. (2013). Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 123:2447-2463.
  2. Le Mercier I, Poujol D, Sanlaville A, Sisirak V, Gobert M, Durand I, Dubois B, Treilleux I, Marvel J, Vlach J, Blay JY, Bendriss-Vermare N, Caux C, Puisieux I, Goutagny N. (2013). Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7 ligand treatment. Cancer Res. 73:4629-4640
  3. El Sayadi H, Pissaloux D, Alberti L, Tabone-Eglinger S, Ranchere D, Decouvelaere AV, Tabone E, Ray-Coquard I, Caux C, Fayette J, Blay JY.  (2013) Autocrine role for Gas6 with Tyro3 and Axl in leiomyosarcomas. Target Oncol. 8:261–269
  4. Bachet JB, Tabone-Eglinger S, Dessaux S, Besse A, Brahimi-Adouane S, Emile JF, Blay JY, Alberti L. (2013). Gene expression patterns of hemizygous and heterozygous KIT mutations suggest distinct oncogenic pathways: a study in NIH3T3 cell lines and GIST samples. PLoS One. 8:e61103
  5. Peron J, Cropet C, Tredan O, Bachelot T, Ray-Coquard I,  Clapisson  G, Chabaud S, Philip I, Borg C, Cassier P, Labidi Galy I, Sebban C, Perol D, Biron P, Caux C, Ménétrier-Caux C, Blay JY. (2013) CD4 lymphopenia to identify end-of-life metastatic cancer patients. Eur J Cancer 49:1080-1089.
  6. Sisirak V, Vey N, Goutagny N, Renaudineau S, Malfroy M, Thys S, Treilleux I, Labidi-Galy SI, Bachelot T, Dezutter-Dambuyant C, Ménétrier-Caux C, Blay JY, Caux C, and Bendriss-Vermare N.  (2013) Breast cancer-derived TGF-b and TNF-a compromise IFN-a production by tumor-associated plasmacytoid dendritic cells. Int J Cancer. 133:771-778.
  7. Faget J, Sisirak V, Blay JY, Caux C, Bendriss-Vermare N, and Ménétrier-Caux C. (2013) ICOS is associated with poor prognosis through immuno-suppressive CD4 T cell amplification by plasmacytoid DC in breast tumours. OncoImmunology 2:e23185
  8. Sisirak V, Faget J, Vey N, Blay JY, Ménétrier-Caux C, Caux C and Bendriss-Vermare N.  (2013) Plasmacytoid dendritic cells deficient in IFNα production promote the amplification of FOXP3+ regulatory T cells and are associated with poor prognosis in breast cancer patients OncoImmunology 2:e22338.
  9. Tredan O, Manuel M, Clapisson G, Bachelot T, Chabaud S, Bardin-dit-Courageot C, Rigal C, Biota C, Bajard A, Pasqual N, Blay JY, Caux C and Ménétrier-Caux C. (2013). Patients with metastatic breast cancer leading to CD4+ T cell Lymphopenia have poor outcome. Eur J Cancer 49:1673-1682.2012

2012 

  1. Caux C. and Zitvogel L. Recent successes of cancer immunotherapy: a new dimension in personalized medicine? Targeted Oncol.  7:1-2, 2012.
  2. Goutagny N, Estornes Y, Hasan U, Lebecque S, Caux C. Targeting Pattern Recognition Receptors in cancer immunotherapy. Targeted Oncol. 7:29-54, 2012.
  3. Labidi-Galy S.I., Treilleux I., Goddard-Léon S., Combes J.D., Blay J.Y., Ray-Coquard I., Caux C., and Bendriss-Vermare N. Plasmacytoid dendritic cells infiltrating ovarian cancer are associated with poor prognosis. OncoImmunology, 1(3):379-81, 2012.
  4. Manuel M, Tredan O, Bachelot T, Clapissson G, Courtier A, Parmentier G, Rabeony T, Grives A, Perez S, Mouret JF, Perol D, Chabaud S, Ray-Coquard I, Labidi-Galy I, Heudel P, Pierga JY, Caux C, Blay JY and Ménétrier-Caux C. Lymphopenia Combined with low TCR Diversity (divpenia) predicts poor Overall Survival in Metastatic Breast Cancer Patient. OncoImmunology, 1(4):433-42, 2012.
  5. Marabelle A,Caux C. Immunobiology. Combined targeted and immunotherapy: the future of personalized medicine. Blood. 2012 Nov 29;120(23):4454-5. doi: 10.1182/blood-2012-09-455105.
  6. Ménétrier-Caux C, Faget J, Biota C, Gobert M, Blay JY and Caux C. Innate immune recognition of breast tumor cells mediates CCL22 secretion favoring Treg recruitment within tumor environment. OncoImmunology, 1(5):759-61, 2012.
  7. Ménétrier-Caux C, Curiel T, Faget J, Manuel M, Caux C and Zou W. Targeting regulatory T cells. Targeted Oncol. 7:15-28, 2012.
  8. Morel AP, Hinkal GW, Thomas C, Fauvet F, Courtois-Cox S, Wierinckx A, Devouassoux-Shisheboran M, Treilleux I, Tissier A, Gras B, Pourchet J, Puisieux I, Browne GJ, Spicer DB, Lachuer J, Ansieau S and Puisieux A. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. Plos Genetics. 8(5): e1002723, 2012.
  9. Peron J, Cropet C, Tredan O, Bachelot T, Ray-Coquard I, Clapisson G, Chabaud S, Philip I, Borg C, Cassier P, Labidi Galy I, Sebban C, Perol D, Biron P, Caux C, Ménétrier-Caux C, Blay JY CD4 lymphopenia to identify end-of-life metastatic cancer patients. Eur J Cancer 2012.
  10. Ray-Coquard I, Chauvin F., Leblanc E.  Caux C., Hoarau H., Bonnetain F, Christophe V, Sastre-Garau X, Lazennec G, Poulain L, Haie-Meder C, Pujade-Lauraine E, Salzet M, Deutsch E, Devouassoux M, Penault Llorca F, Lecuru F, Taieb S, Arveux P, Theillet C, Joly F. Le PAIR-gynécologie : recherche multi/interdisciplinaire en cancérologie gynécologique. Les problèmes à résoudre en 2012. Bull Cancer. 99(4):479-498, 2012.
  11. Trédan O, Manuel M, Clapisson G, Bachelot T, Chabaud S, Bardin-Dit-Courageot C, Rigal C, Biota C, Bajard A, Pasqual N, Blay JY, Caux C, Ménétrier-Caux C. Patients with metastatic breast cancer leading to CD4(+) T cell lymphopaenia have poor outcome. Eur J Cancer. 2012 Dec 19.
  12. Segura E., Valladeau-Guilemond J., Donnadieu MH, Sastre-Garau X, Soumelis V, Amigorena S. Characterization of resident and migratory dendritic cells in human lymph nodes. J Exp Med. 209:653-60, 2012.

2011

  1. Cassier PA, Treilleux I, Bachelot T, Ray-Coquard I, Bendriss-Vermare N, Menetrier-Caux C, Tredan O, Goddard-Leon S, Pin JJ, Mignotte H, Barthelemy-Dubois C, Caux C, Lebecque S, Blay JY. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer. BMC Cancer. 11:213-23, 2011.
  2. Delahaye NF, Rusakiewicz S, Martins I, Ménard C, Roux S, Lyonnet L, Paul P, Sarabi M, Chaput N, Semeraro M, Minard-Colin V, Poirier-Colame V, Chaba K, Flament C, Baud V, Authier H, Kerdine-Römer S, Pallardy M, Cremer I, Peaudecerf L, Rocha B, Valteau-Couanet D, Gutierrez JC, Nunès JA, Commo F, Bonvalot S, Ibrahim N, Terrier P, Opolon P, Bottino C, Moretta A, Tavernier J, Rihet P, Coindre JM, Blay JY, Isambert N, Emile JF, Vivier E, Lecesne A, Kroemer G, Zitvogel L. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nat Med. 17:700-7, 2011.
  3. Faget J., Biota C., Bachelot T., Gobert M., Treilleux I., Goutagny N., Durand I., Léon-Goddard S.,  Blay J.Y., Caux C. and Ménétrier-Caux C. Early detection of tumor cells by innate immune cells leads to Treg recruitment through CCL22 production by tumor cells. Cancer Res. 71:6143-52, 2011.
  4. Gougelet A, Perez J, Pissaloux D, Besse A, Duc A, Decouvelaere AV, Ranchere-Vince D, Blay JY, Alberti L. miRNA Profiling: How to Bypass the Current  Difficulties in the Diagnosis and Treatment of Sarcomas. Sarcoma. 2011:1-14, 2011.
  5. Labidi-Galy SI, Ray-Coquard I, Sisirak V, Treilleux I, Meeus P, Mithieux F, Bajard A, Combes JD, Gobert M, Faget J, Guastalla JP, Tredan O, Ménétrier-Caux C, Caux C, Blay JY and Bendriss-Vermare N.Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer. Cancer Res. 171:5423-34, 2011.
  6. Labidi-Galy S.I., Faget J., Treilleux I., Ménétrier-Caux C., Caux C., and Bendriss-Vermare N. Immunologie du cancer de l’ovaire : de la théorie à la thérapeutique. "Cancer de l’ovaire" Edition 2, (Edition : Springer), chapter book, pp 613-626, 2011.
  7. Perez J., Bardin C., Rigal C., Besse A., Rousseau R., and Dutour A. Anti MDR1 siRNA restores chemosensitivity in chemoresistant breast carcinoma and osteosarcoma cell lines. Anticancer Res. 31(9):2813-20, 2011.
  8. Sisirak V, Vey N, Vanbervliet B, Duhen T, Puisieux I, Homey B, Bowman EP, Trinchieri G, Dubois B,  Kaiserlian D, Lira SA, Puisieux A, Blay JY, Caux C, and Bendriss-Vermare N. CCR6/CCR10-mediated plasmacytoid dendritic cells recruitment to inflamed epithelia following instruction in lymphoid organs. Blood. 118(19):5130-40, 2011.

BREVET: Antibodies directed against ICOS and uses thereof. Filed May 2011, n° EP11305385.5. Inventors: JULIEN FAGET, MÉNÉTRIER-CAUX CHRISTINE, JACQUES NUNES, DANIEL OLIVE, CAUX CHRISTOPHE

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