News
Seminar

Mardi 19 Décembre 2023 de 11h00 à 12h30
SEMINAIRE IRCM MARDI 19 DECEMBRE 11h


 Lluis Fajas Coll

Center for Integrative Genomics, CIG / UNIL Sorge
CH1015 Lausanne Switzerland

"Highway to hell or stairway to heaven: The CDK4 paradox in triple negative breast cancer"

contact : Claude Sardet (IRCM)


Vendredi 15 Décembre 2023 de 14h00 à 15h30
SEMINAIRE IRCM VENDREDI 15 DECEMBRE


Charline OGIER, PhD

Centre 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.

Mercredi 08 Novembre 2023 de 11h00 à 12h15
SEMINAIRE Labex MabImprove


Docteur Renaud LESOURNE

Institut Toulousain des Maladies Infectieuses et Inflammatoires

" Signaling modulation of immune checkpoints in T cells in normal and autoimmune contexts "

contact : M.A. Poul (IRCM)


Vendredi 12 Janvier 2024 de 14h00 à 15h15
SEMINAIRE VENDREDI 12 JANVIER 2024


Vincent Muczynski

Director 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)


Vendredi 02 Février 2024 de 14h00 à 15h15
SEMINAIRE VENDREDI 02 FEVRIER 2024 à 14h


Sergio Casas Tintó

Instituto 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)


Vendredi 08 Décembre 2023 de 14h00 à 15h00
SEMINAIRE IRCM/MASTER CANCER BIOLOGY


Olivier Adotévi

PU-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


Jeudi 09 Novembre 2023 de 14h00 à 15h00
SEMINAIRE IRCM/MASTER CANCER BIOLOGY


Vanja Sisirak

CNRS Research Scientist (CRCN)
Immuno-ConcEpT Team, CNRS UMR 5164
URL: https://www.immuconcept.org/team_member/vanja-sisirak/

"Role of DNASEs in the regulation of self DNA immunostimmulatory potential in health and disease”

contacts : Julien Faget ou Marie-Alix Poul ou Julie Constanzo (IRCM)


Vendredi 09 Février 2024 de 14h00 à 15h00
SEMINAIRE IRCM 09 fevrier 2024



Vendredi 19 Janvier 2024 de 14h00 à 15h30
SEMINAIRE IRCM VENDREDI 19 JANVIER 2024


Etienne BECHT

Centre 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)


Jeudi 05 Octobre 2023 de 14h00 à 15h15
SEMINAIRE IRCM JEUDI 05 OCTOBRE 14h


Mutita JUNKING, PhD

Assistant Professor Molecular Biology, Siriraj Hospital, Mahidol University (Thailand)

Chimeric Antigen Receptor T Cells Targeting CD19 and Secreting Anti-PD-L1 Single Chain Variable Fragment Reduce PD-L1-induced T Cell Exhaustion

host: Emmanuel Cornillot (Montpellier University-IRCM)

Dr. Mutita Junking is an Assistant Professor of Molecular Biology within the
Research Department at the Faculty of Medicine, Siriraj Hospital, Mahidol
University. She also holds the position of Head of the Division of Molecular
Medicine in the Research Department and is the Deputy Director of the Siriraj
Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT).Her research focus on the advancing cellular immunotherapy for cancertreatment. Her research group has developed protocols and published data related to dendritic cell-induced anti-tumor T cells.They have also made
significant strides in developing chimeric antigen receptor (CAR) T cells
targeting tumor-associated antigens across various cancer models, including
hematologic malignancies and solid tumors. Dr. Mutita is dedicated to
pushing the boundaries in CAR T cell research, aspiring to create the next
generation of CAR T cells that are not only more effective but also hold
immense potential for treating cancer patients.

Résumé Séminaire :

Adoptive T cell therapy utilizing second-generation anti-CD19 chimeric
antigen receptor (anti-CD19-CAR2) T cells has achieved complete
remission in heavily pretreated patients with B cell acute lymphoblastic
leukemia (B-ALL) or diffuse large B cell lymphoma (DLBCL). However, the
clinical efficacy in aggressive B cell lymphomas (BCL) has been suboptimal
due to programmed cell death protein 1 ligand (PD-L1) expressed on BCL
cells binding to the PD-1 receptor on T cells, leading to limited T cell
function. We designed and generated anti-CD19-CAR4-T cells that secrete
anti-PD-L1 single-chain variable fragment (scFv), referred to as anti-CD19-
CAR5-T cells. Both anti-CD19-CAR-T cell types feature an anti-CD19 scFv
derived from monoclonal antibody, coupled with CD28/4-1BB/CD27/CD3ζ
f or enh anced f unc tion alit y. The ant i-PD-L1 scFv o rig in at es from
atezolizumab and demonstrated the ability to bind to PD-L1, inhibiting the
binding of anti-PD-L1 monoclonal antibodies to PD-L1high cancer cells. In
vitro evaluations showed that both anti-CD19-CAR4-T and anti-CD19-
CAR5-T cells efficiently targeted and killed CD19+ cancer cells in 2D and
3D co-culture systems. Interestingly, anti-CD19-CAR5-T cells displayed
superior proliferative capacity. At a low effector (E) to target (T) ratio of
0.5:1, anti-CD19-CAR5-T cells exhibited higher cytotoxicity against
CD19+/PD-L1high cells compared to anti-CD19-CAR4-T cells. Notably, the
cytotoxicity of anti-CD19-CAR4-T cells against CD19+/PD-L1high cells could
be restored by supplementing anti-PD-L1 scFv. Our findings highlight the
promising combination antitumor efficacy of anti-CD19-CAR4-T cells and
anti-PD-L1 scFv against CD19+/PD-L1high tumors. As a result, anti-CD19-
CAR5-T cells warrant further investigation in terms of in vivo antitumor
efficiency and potential inclusion in clinical trials as a treatment for
aggressive B cell lymphoma.

 


Vendredi 29 Septembre 2023 à 14h00
SEMINAIRE VENDREDI 29 SEPTEMBRE A 14h


Jonathan Reboulet

LiPiCS Services (Lyon-France)

"Application of a  new protein-protein interactions screening technology to decipher oncoprotein interactomes and their alterations by mutations, drugs and peptides."

contact : Eric JULIEN (CNRS/Inserm)

Protein-protein interactions are a key factor to understand a protein function. As we tried to identify molecular mechanisms explaining the pro and anti-tumoral effect of a well known transcription family, we developped a Bimolecular Fluorescence Complementation based asssay to screen in live cell line for whole interactome of a target. Reaching higher robustness than other screening technology, we performed comparative analysis to understand the effect of differents effectors and mutations on target interactome.


Vendredi 10 Novembre 2023 de 14h00 à 16h00
SEMINAIRE VENDREDI 10 NOVEMBRE 14h


Elodie LALLET

INTEGRAGEN, Genopole Campus, Evry (Paris)

"Innovation en analyses et tests Génomiques : nouvelles avancées en oncologie"

contact : Pierre-François ROUX (equipe L. LeCam-INSERM)



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