from concepts to biomarkers

& innovations in precision medicine

17 research teams,

9 platforms, 3 hosted biotechs

our state-of-the-art tools,

for cancer research

in the heart of a campus dedicated to applied cancer research...

...and Montpellier,

a city historically linked to medical research and teaching

the IRCM research teams
the IRCM research teams

L'Institut de Recherche en Cancérologie de Montpellier :
«Together, let's push the boundaries»

News

Postdoctoral Position in cell matrix biology & antibody-drug conjugate

Publié le 07 Décembre 2023Postdoctoral Position in cell matrix biology & antibody-drug conjugate Application deadline: 31 January, 2024Anticipated start date: ASAP 2024The team (Breast cancer, Microenvironment and Immunotargeting) at Montpellier Cancer Research Institute (France) is looking for a postdoctoral researcher to work on the optimization of antibody-drug conjugates targeting matricellular proteins in breast cancer. This postdoctoral fellowship is part of a priority research program and equipment (PEPR) ACCREDIA, which brings together a lab network of seven academic partners funded by the French government to improve knowledge, skills and methodologies in antibody development. The position is funded in the frame of French PEPR-PIA4 Accredia ANR-22-PEBI-0009 for a period of 2 to 3 years. More
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Postdoctoral Position in Antibody Engineering

Publication le Vendredi 01 Décembre 2023The team Functional screening and targeting in cancer located at Montpellier Cancer Research Institute (France) is seeking a postdoctoral researcher to work on the development of new methods to improve antibody and bispecific developability and expression. The position is funded in the frame of French PEPR ACCREDIA for a period of 2 to 3 years. More information
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SEMINAIRE IRCM MARDI 19 DECEMBRE 11h

 Lluis Fajas CollCenter for Integrative Genomics, CIG / UNIL SorgeCH1015 Lausanne Switzerland"Highway to hell or stairway to heaven: The CDK4 paradox in triple negative breast cancer"contact : Claude Sardet (IRCM)
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SEMINAIRE IRCM VENDREDI 15 DECEMBRE

Charline OGIER, PhDCentre de Recherche en Cancérologie de Toulouse (CRCT)-UMR 1037 "Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6)"contact : Christel Larbouret (Inserm-IRCM) The fibroblastic stroma comprises most of pancreatic adenocarcinoma mass and is remarkably devoid of functional blood vessels leaving an unresolved question of how pancreatic cancer cells obtain their essential metabolites and especially water-insoluble lipids. Contrary to the previously held assumption that cancer cells uptake lipids directly from the interstitial fluid, we have found a critical role for cancer-associated fibroblasts (CAFs) to obtain and transfer blood-borne lipid particles to cancer cells via trogocytosis, a process of “nibbling” of plasma membranes between two cells engaged in synapse-like membrane contacts. Whereas trogocytosis has been described in normal development, the biochemical and signaling regulators of trogocytosis between CAFs and PDAC cells have not been defined. We determined that CAF membrane trogocytosis is triggered by externalized phosphatidylserine (PtdSer), and blockade of PtdSer in vitro transiently deters trogocytic uptake of CAF membranes. We have also discovered a phospholipid scramblase anoctamin 6 (ANO6) expressed in CAFs as the essential trogocytosis regulator to promote cancer cell survival. Mechanistically, CAF-cancer cell membrane contacts induce cytosolic calcium influx via Orai channels, which activates ANO6 and results in phosphatidylserine exposure on CAFs. As a promising therapy target, ANO6 protein is highly expressed in PDAC tumor mass in cancer cells, endothelial cells and CAFs and is a negative prognostic biomarker for survival. Depletion of ANO6 in co-implanted CAFs dramatically reduced the growth of orthotopic pancreatic tumor grafts. Furthermore, pharmacologic inhibitors of ANO6 with clinically available antibiotics niclosamide or clofazimine potently blocked cholesterol uptake in vivo by PDAC cells.  Our findings indicate a novel trogocytosis function for CAFs in highly desmoplastic carcinomas as the main mechanism of lipids delivery to cancer cells. CAFs do so by expressing PtdSer as “eat me” signals. This process is regulated by Ca2+-dependent phospholipid scramblase ANO6. Re-purposing of clinically available ANO6 inhibitors could make a tangible impact on treatment of PDAC patients in the near term.
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SEMINAIRE VENDREDI 12 JANVIER 2024

Vincent MuczynskiDirector of Biology, NovalGen Ltd  / Research Fellow, University College London – Cancer Institut"Next-generation bispecific T cell engagers with built-in autoregulation to prevent treatment-related adverse events in adoptive T cell immunotherapies."contact : P. Martineau (IRCM)
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SEMINAIRE VENDREDI 02 FEVRIER 2024 à 14h

Sergio Casas TintóInstituto de Investigación de Enfermedades Raras (IIER-ISCIII) / Unidad de Enfermedades Humanas en Drosophila (MEHD). Madrid “Cell to cell communication in glioblastoma progression”contact : A/ Maraver (IRCM)
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SEMINAIRE IRCM/MASTER CANCER BIOLOGY

Olivier AdotéviPU-PH, rattaché à l’Université de Franche-Comté.Directeur de l’unité INSERM U1098 RIGHT à Besançon.« CD4 T cells stimulation for therapeutic cancer vaccines success »contact : Julien Faget ou Marie-Alix Poul ou Julie Constanzo
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Félicitations à Ghita Chabab, lauréate du second prix de thèse de l'ED CBS2, prix récompensant les trois meilleures thèses soutenues au cours de l'année 2022. Sa thèse a concerné la caractérisation d'une sous-population de LT ?? régulateurs dans les cance

Félicitations à Ghita Chabab, lauréate du second prix de thèse de l'ED CBS2, prix récompensant les trois meilleures thèses soutenues au cours de l'année 2022 ! Sa thèse a concerné la caractérisation d’une sous-population de LT γδ régulateurs dans les cancers solides humains. Ce travail a été réalisé dans l'équipe Immunité et Cancer à l'IRCM sous la direction de Virginie Lafont.
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SEMINAIRE IRCM 09 fevrier 2024

Eric CHEVETINSERM U1242, Université de Rennes, Rennes, France. Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France."Targeting Endoplasmic Reticulum proteostasis in cancer"host : Antonio Maraver (IRCM-Inserm)Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor aggressiveness. Genetic and pharmacological evidence suggest that the endoplasmic reticulum (ER), a major site for protein folding and quality control, plays a critical role in cancer development. This concept has been validated in triple negative breast cancer, prostate cancer as well as in glioblastoma multiform (GB), the most lethal primary brain cancer with an overall survival of 15 months and no effective treatment. We demonstrated that the ER stress sensor IRE1 contributes to GB progression, impacting tissue invasion and tumor vascularization. IRE1 is a dual Kinase/RNase that signals by catalyzing the non-conventional splicing of the mRNA encoding the transcription factor XBP1, and in addition by regulating RNA stability through a process known as Regulated IRE1 Dependent Decay (RIDD). We further investigated the contribution of IRE1 signaling to GB and defined a specific expression signature that when confronted to human GB transcriptomes showed the antagonistic roles of XBP1 mRNA splicing and RIDD on tumor characteristics and outcomes. Moreover, using this signature we have explored the role of IRE1 signaling in tumor cells in reshaping the tumor microenvironment. These data identified IRE1 as an actionable therapeutic target which allowed us to use develop pharmacological approaches to enhance the efficacy of GB standard of care in mouse models.
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SEMINAIRE IRCM VENDREDI 19 JANVIER 2024

Etienne BECHTCentre de Recherche sur l'Inflammation - UMRS 1139 INSERM (PARIS)"High-throughput quantification of 100s of proteins using flow cytometry and machine learning"contact : P. MARTINEAU (IRCM-Inserm)
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the word of the director

"Together, let's push the limits."

"In barely 20 years, the Institut de Recherche en Cancérologie de Montpellier (IRCM U1194) has succeeded in raising its research to the highest international level in the field of fundamental and applied cancer research, carried out in close collaboration with the clinical departments of the Montpellier Cancer Center (ICM: l'Institut du Cancer de Montpellier), and industrial partners. Under the joint supervision of Inserm, the ICM and the University of Montpellier, the IRCM brings together more than 240 people, researchers, clinicians, technicians and students, organized in 16 research teams that rely on high-performance technical platforms and competent support services. In an extremely competitive and rapidly evolving field of research, our greatest challenge is to stay one step ahead. To do so, we will continue to structure cancer research in Montpellier, to seek excellence and to accelerate innovation and transfer to the patient in order to ultimately contribute to overcoming the countless different forms of cancer. Together, let's push the limits"

Nathalie Bonnefoy, Director of the IRCM

the word of the director

MAIN PUBLICATIONS

Bousquet Mur E, Bernardo S, Papon L, Mancini M, Fabbrizio E, Goussard M, Ferrer I, Giry A, Quantin X, Pujol J-L, Calvayrac O, Moll H, Glasson Y, Pirot N, Turtoi A, Cañamero M, Wong K-K, Yarden Y, Casanova E, Soria J-C, Colinge J, Siebel C, Favre G, Paz-Ares L, Maraver A Notch inhibition overcomes resistance to Tyrosine Kinase Inhibitors in EGFR-driven lung adenocarcinoma. J. Clin. Invest.. Oct 31, 2019. doi:10.1172/JCI126896

Combes E, Andrade A, Tosi D, Michaud H-A, Coquel F, Desigaud D, Jarlier M, Coquelle A, Pasero P, Bonnefoy N, Martineau P, Del Rio M, Beijersbergen R, Vezzio-Vie N Inhibition of Ataxia-Telangiectasia Mutated and RAD3-related (ATR) overcomes oxaliplatin resistance and promotes anti-tumor immunity in colorectal cancer. Cancer Res.. Apr 15, 2019. doi:10.1158/0008-5472.CAN-18-2807

Ashraf Y, Mansouri H, Laurent-Matha V, Alcaraz L, Roger P, Guiu S, Derocq D, Robin G, Michaud H-A, Jarlier M, Pugnière M, Robert B, Puel A, Martin L, Landomiel F, Bourquard T, Achour O, Fruitier-Arnaudin I, Pichard A, Deshayes E, Turtoi A, Poupon A, Boissière-Michot F, Pirot N, Bernex F, Jacot W, du Manoir S, Theillet C, Pouget J-P, Navarro-Teulon I, Bonnefoy N, Pèlegrin A, Chardès T, Martineau P, Liaudet-Coopman E Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies. J Immunother Cancer. 2019;7(1):29. doi:10.1186/s40425-019-0498-z

Perrot I, Michaud H-A, Giraudon-Paoli M, Augier S, Docquier A, Gros L, Courtois R, Jecko D, Becquart O, Rispaud-Blanc H, Gauthier L, Rossi B, Chanteux S, Gourdin N, Amigues B, Roussel A, Bensussan A, Eliaou J-F, Bastid J, Romagné F, Morel Y, Narni-Mancinelli E, Vivier E, Paturel C, Bonnefoy N Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies. Cell Rep. 2019;27(8):2411-2425.e9. doi:10.1016/j.celrep.2019.04.091

Forest E, Logeay R, Géminard C, Kantar D, Frayssinoux F, Heron-Milhavet L, Djiane A The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs. J. Cell Biol.. 2018;217(3):1047-1062. doi:10.1083/jcb.201705107

Arena G, Cissé M, Pyrdziak S, Chatre L, Riscal R, Fuentes M, Arnold J, Kastner M, Gayte L, Bertrand-Gaday C, Nay K, Angebault-Prouteau C, Murray K, Chabi B, Koechlin-Ramonatxo C, Orsetti B, Vincent C, Marine J-C, Etienne-Manneville S, Bernex F, Lombès A, Cameron C, Dubouchaud H, Ricchetti M, Linares L, Le Cam L Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53. Mol. Cell. 2018;69(4):594-609.e8. doi:10.1016/j.molcel.2018.01.023

Leconet W, Chentouf M, du Manoir S, Chevalier C, Sirvent A, Aït-Arsa I, Busson M, Jarlier M, Radosevic-Robin N, Theillet C, Chalbos D, Pasquet J-M, Pèlegrin A, Larbouret C, Robert B Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis. Clin. Cancer Res.. 2017;23(11):2806-2816. doi:10.1158/1078-0432.CCR-16-1316

Brustel J, Kirstein N, Izard F, Grimaud C, Prorok P, Cayrou C, Schotta G, Abdelsamie A, Déjardin J, Méchali M, Baldacci G, Sardet C, Cadoret J-C, Schepers A, Julien E Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication. EMBO J.. 2017;36(18):2726-2741. doi:10.15252/embj.201796541


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