Vendredi 08 Décembre 2023 de 14h00 à 15h00

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

Vendredi 15 Décembre 2023 de 14h00 à 15h30

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.

Vendredi 12 Janvier 2024 de 14h00 à 15h15

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 19 Janvier 2024 de 14h00 à 15h30

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)

Vendredi 02 Février 2024 de 14h00 à 15h15

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


INSERM 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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