Tumour immunology and immunotherapy

Tumour immunology and immunotherapy

Group 1 of the Inserm (National Institute of Health and Medical Research) UMR 1015 research unit, « Tumour immunology and immunotherapy of cancer », is under the direction of Professor Laurence Zitvogel.  Between 2015 and 2018 it will be exploring three lines of research: 
-    Gut microbiota and pro- or anti-tumour inflammatory/immunological activity, by measuring the effect of specific therapies on their regulation, 
-    Individualised immunotherapy with monoclonal antibodies tailored according to the tumour microenvironment (varying as a function of the histology and the patient). The mode of action of these immunomodulators will be studied and tests to predict the response to these antibodies or combinations of them will be developed, 
-    Characterisation of NK (natural killer) cells invading tumours: their role, specific receptors and differentiation.   

The CICBT507 (CICBT = Centre for Clinical Investigation in Biotherapies of Cancer) unit under the triple aegis of the Gustave Roussy Institute, the Curie Institute and INSERM plans to develop novel therapeutic approaches in immuno-oncology, using new animal models and immunomonitoring tools. This group will be working closely with the Cellular Therapy Unit (in particular using dendritic cell-derived exosomes) and will be involved in Phase I-II-III clinical trials planned in our centres.

• Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.
  Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L.
  Science. 2018 Jan 5;359(6371):91-97. doi: 10.1126/science.aan3706. Epub 2017 Nov 2.
• Predictors of responses to immune checkpoint blockade in advanced melanoma.
  Jacquelot N, Roberti MP, Enot DP, Rusakiewicz S, Ternès N, Jegou S, Woods DM, Sodré AL, Hansen M, Meirow Y, Sade-Feldman M, Burra A, Kwek SS, Flament C, Messaoudene M, Duong CPM, Chen L, Kwon BS, Anderson AC, Kuchroo VK, Weide B, Aubin F, Borg C, Dalle S, Beatrix O, Ayyoub M, Balme B, Tomasic G, Di Giacomo AM, Maio M, Schadendorf D, Melero I, Dréno B, Khammari A, Dummer R, Levesque M, Koguchi Y, Fong L, Lotem M, Baniyash M, Schmidt H, Svane IM, Kroemer G, Marabelle A, Michiels S, Cavalcanti A, Smyth MJ, Weber JS, Eggermont AM, Zitvogel L.
  Nat Commun. 2017 Sep 19;8(1):592. doi: 10.1038/s41467-017-00608-2.    
• Immune biomarkers for prognosis and prediction of responses to immune checkpoint blockade in cutaneous melanoma.
  Jacquelot N, Pitt JM, Enot DP, Roberti MP, Duong CPM, Rusakiewicz S, Eggermont AM, Zitvogel L.
  Oncoimmunology. 2017 Mar 7;6(8):e1299303. doi: 10.1080/2162402X.2017.1299303. eCollection 2017. Review.
• [Gut microbiota and efficacy of cancer therapies].
  Vétizou M, Daillère R, Zitvogel L.
  Biol Aujourdhui. 2017;211(1):51-67. doi: 10.1051/jbio/2017009. Epub 2017 Jul 6. French.    
• Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAF^v600e Melanoma Lines with Vemurafenib.
  Frazao A, Colombo M, Fourmentraux-Neves E, Messaoudene M, Rusakiewicz S, Zitvogel L, Vivier E, Vély F, Faure F, Dréno B, Benlalam H, Bouquet F, Savina A, Pasmant E, Toubert A, Avril MF, Caignard A.
  Cancer Immunol Res. 2017 Jul;5(7):582-593. doi: 10.1158/2326-6066.CIR-16-0380. Epub 2017 Jun 2.    
• Anticancer effects of the microbiome and its products.
  Zitvogel L, Daillère R, Roberti MP, Routy B, Kroemer G.
  Nat Rev Microbiol. 2017 Aug;15(8):465-478. doi: 10.1038/nrmicro.2017.44. Epub 2017 May 22. Review.    
• Prognostic impact of the expression of NCR1 and NCR3 NK cell receptors and PD-L1 on advanced non-small cell lung cancer.
  Fend L, Rusakiewicz S, Adam J, Bastien B, Caignard A, Messaoudene M, Iribarren C, Cremer I, Marabelle A, Borg C, Semeraro M, Barraud L, Limacher JM, Eggermont A, Kroemer G, Zitvogel L.
  Oncoimmunology. 2016 May 13;6(1):e1163456. doi: 10.1080/2162402X.2016.1163456. eCollection 2017.    
• NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.
  Rusakiewicz S, Perier A, Semeraro M, Pitt JM, Pogge von Strandmann E, Reiners KS, Aspeslagh S, Pipéroglou C, Vély F, Ivagnes A, Jegou S, Halama N, Chaigneau L, Validire P, Christidis C, Perniceni T, Landi B, Berger A, Isambert N, Domont J, Bonvalot S, Terrier P, Adam J, Coindre JM, Emile JF, Poirier-Colame V, Chaba K, Rocha B, Caignard A, Toubert A, Enot D, Koch J, Marabelle A, Lambert M, Caillat-Zucman S, Leyvraz S, Auclair C, Vivier E, Eggermont A, Borg C, Blay JY, Le Cesne A, Mir O, Zitvogel L.
  Oncoimmunology. 2016 Apr 25;6(1):e1137418. doi: 10.1080/2162402X.2015.1137418. eCollection 2017.
• Enhancing the clinical coverage and anticancer efficacy of immune checkpoint blockade through manipulation of the gut microbiota.
  Pitt JM, Vétizou M, Gomperts Boneca I, Lepage P, Chamaillard M, Zitvogel L.
  Oncoimmunology. 2016 Feb 18;6(1):e1132137. doi: 10.1080/2162402X.2015.1132137. eCollection 2017.
• NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution.
  Messaoudene M, Fregni G, Enot D, Jacquelot N, Neves E, Germaud N, Garchon HJ, Boukouaci W, Tamouza R, Chanal J, Avril MF, Toubert A, Zitvogel L, Rusakiewicz S, Caignard A.
  Oncoimmunology. 2016 Mar 10;5(12):e1154251. doi: 10.1080/2162402X.2016.1154251. eCollection 2016.    
• [The role of intestinal microbiota in the response to anti-tumor therapies].
  Vétizou M, Daillère R, Zitvogel L.
  Med Sci (Paris). 2016 Nov;32(11):974-982. doi: 10.1051/medsci/20163211013. Epub 2016 Dec 23. Review. French.    
• The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ.
  Semeraro M, Adam J, Stoll G, Louvet E, Chaba K, Poirier-Colame V, Sauvat A, Senovilla L, Vacchelli E, Bloy N, Humeau J, Buque A, Kepp O, Zitvogel L, André F, Mathieu MC, Delaloge S, Kroemer G.
  Oncoimmunology. 2016 Aug 18;5(10):e1218106. eCollection 2016.    
• Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects.
  Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, Duong CPM, Flament C, Lepage P, Roberti MP, Routy B, Jacquelot N, Apetoh L, Becharef S, Rusakiewicz S, Langella P, Sokol H, Kroemer G, Enot D, Roux A, Eggermont A, Tartour E, Johannes L, Woerther PL, Chachaty E, Soria JC, Golden E, Formenti S, Plebanski M, Madondo M, Rosenstiel P, Raoult D, Cattoir V, Boneca IG, Chamaillard M, Zitvogel L.
  Immunity. 2016 Oct 18;45(4):931-943. doi: 10.1016/j.immuni.2016.09.009. Epub 2016 Oct 4.    
• [Chemokine receptors expression on T cells: contribution to diagnosis of melanoma metastasis dissemination status].
  Jacquelot N, Enot DP, Flament C, Dalle S, Zitvogel L.
  Med Sci (Paris). 2016 8-9;32(8-9):690-2. doi: 10.1051/medsci/20163208010. Epub 2016 Sep 12. French. No abstract available.    
• Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome.
  Pitt JM, Vétizou M, Waldschmitt N, Kroemer G, Chamaillard M, Boneca IG, Zitvogel L.
  Cancer Res. 2016 Aug 15;76(16):4602-7. doi: 10.1158/0008-5472.CAN-16-0448. Epub 2016 Jul 29. Review.    
• Biomarkers of immunogenic stress in metastases from melanoma patients: Correlations with the immune infiltrate.
  Ladoire S, Senovilla L, Enot D, Ghiringhelli F, Poirier-Colame V, Chaba K, Erdag G, Schaefer JT, Deacon DH, Zitvogel L, Slingluff CL Jr, Kroemer G.
  Oncoimmunology. 2016 Mar 16;5(6):e1160193. doi: 10.1080/2162402X.2016.1160193. eCollection 2016 Jun.    
• Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors.
  Pitt JM, Vétizou M, Daillère R, Roberti MP, Yamazaki T, Routy B, Lepage P, Boneca IG, Chamaillard M, Kroemer G, Zitvogel L.
  Immunity. 2016 Jun 21;44(6):1255-69. doi: 10.1016/j.immuni.2016.06.001. Review.    
• Unchaining NK cell-mediated anticancer immunosurveillance.
  Zitvogel L, Kroemer G.
  Nat Immunol. 2016 Jun 21;17(7):746-7. doi: 10.1038/ni.3471. No abstract available.    
• Microbiome and Anticancer Immunosurveillance.
  Zitvogel L, Ayyoub M, Routy B, Kroemer G.
  Cell. 2016 Apr 7;165(2):276-87. doi: 10.1016/j.cell.2016.03.001. Review.
• Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy.
  Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, Zitvogel L.
  Ann Oncol. 2016 Aug;27(8):1482-92. doi: 10.1093/annonc/mdw168. Epub 2016 Apr 10. Review.
• The oncolytic peptide LTX-315 overcomes resistance of cancers to immunotherapy with CTLA4 checkpoint blockade.
  Yamazaki T, Pitt JM, Vétizou M, Marabelle A, Flores C, Rekdal Ø, Kroemer G, Zitvogel L.
  Cell Death Differ. 2016 Jun;23(6):1004-15. doi: 10.1038/cdd.2016.35. Epub 2016 Apr 15.

Lab members

Group leader : Pr. Laurence ZITVOGEL

• Nathalie MALHERBE, Assistant manager
• Pierre LY, Laboratory Manager
• Maria SEMEDO DE BRITO, Laboratory agent
• Lisa DEROSA, Oncologist, MCU-PH clinical immunology
• Marine FIDELLE, Pharmacist Assistant specialist at CLCC, Post-Doctoral position
• Isabelle LEBHAR, Project Manager
• Cheick Oumar GUINDO, Clinical Project Manager
• Camille BIGENWALD, Practicing hematologist at CLCC, Post-doctoral position
• Marie XIBERRAS, Laboratory technician
• Mathias MARQUES, Laboratory technician
• Eugénie PIZZATO, Laboratory technician
• Darina BRIGHTON, Laboratory technician
• Jianzhou CHEN, Post-Doctoral position
• Guoxin CAI, Post-Doctoral position
• Ai-Ling TIAN, Post-Doctoral position
• Yasmine HASSANI, Post-Doctoral position
• Fatma BENSEDDIK, Post-Doctoral position
• Cassandra THELEMAQUE, Engineer
• Ella REICH, PhD student
• Simon THOMAS, PhD student
• Anne Laure MALLARD DE LA VARENDE, PhD student
• Déborah SUISSA, PhD student
• Ines DARIK, Engineer
• Eléonore PIARD, Engineer intern
• Axel DUFOUR, Master 2
• Yoan HURTADO, Master 2
• Ombeline BARTHEL, Intern
• Mathieu LOGEROT, Intern