Team 02 - Reprograming tumor activitY and associaTed MicroenvironmEnt (Rytme).

Équipe 02 – Reprogrammation de l’activité tumorale et du microenvironnement associé (Rytme).

The research of the team is mainly dealing with the role of the secretory pathway during tumour initiation and progression, and tumour cells interaction with their microenvironment. Our main objective is to evaluate the potential use of the tumour secretory pathway signalling and associated tumour microenvironment molecules as cancer prognostic markers and/or therapeutic targets.   See interview TV FR3 2021: Subconazol, la molécule anti-Covid-19 transfrontalière du Pays basque

Keywords

AGRs, furin, convertases, Apelin, Elabela, tumoral miroenvironnement, organoids, zebrafish

Projects

Oncology & Gynaecological (OncoGyne) Laboratory

The Oncology & Gynaecology Laboratory (OncoGyne) is dedicated to translational research on malignant gynaecological tumours, in partnership with the Institut Bergonié. Our work aims to deepen the understanding of these cancers and to improve patient care.

 

Our main research areas are as follows:

  • ARTiSt (G. Babin & F. Delom): Understanding the molecular and cellular mechanisms underlying gynaecological tumours.
  • MATRIX (S. Croce & D. Fessart): Enhancing tumour detection and characterisation to improve patient stratification and enable more targeted follow-up.
  • RAPID (F. Guyon): Optimising diagnosis and clinical decision-making through innovative approaches, with a direct impact on therapeutic management.

In addition, through our POETIC platform, we develop tools to quantify biomarkers and screen molecular libraries. This platform helps identify therapeutic targets and validate treatment strategies.

Our projects combine fundamental, translational, and clinical research. They rely on patient cohorts treated at the Institut Bergonié and on preclinical models, including cell lines and patient-derived mouse models. These models allow us to test and validate our fundamental and translational findings.

Keywords: Gynaecological tumours, uterine sarcomas, biomarkers, diagnosis, cell signalling, clinical decision-making, translational research.

Project members
Noteworthy publications
Deep Learning Can Accurately Predict the Prognosis of Gynecologic Smooth Muscle Tumors of Uncertain Malignant Potential: A Multicenter Pilot Study.
Costa J, Le VL, De Leo A, Ravaioli C, Velasco V, Davidson B, Skeie-Jensen T, Devouassoux-Shisheboran M, Trecourt A, Bartosch C, Rios E, Genestie C, Pautier P, Lebreton C, Guyon F, Babin G, Coindre JM, Le Loarer F, Saut O, Croce S
Laboratory investigation; a journal of technical methods and pathology ; 2025 Jun 30
The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features.
Trecourt A, Azmani R, Hostein I, Blanchard L, Le Loarer F, Bourdon A, Alame M, Nadaud B, Mayer L, Rebier F, Larmonier C, Moura MS, Soubeyran I, Hartog C, Ray-Coquard I, Treilleux I, Devouassoux-Shisheboran M, Croce S
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ; 2023 Oct 01
AGR2 protein expression in colorectal tumour epithelialcompartment.
Chevet E, Bassal F, Beq S, Bonhomme B, Boisteau E, Calloch J, Cazals-Hatem D, Delom F, Fessart D, Evrard S, Hrstka R, Hupp T, Lièvre A, Louis E, Mariau J, Meuwis MA, Ogier-Denis E, Paradis V, Pernot S, Pineau R, Treton X, Velasco V, Vieujean S
Gut ; 2022 Dec 09
Integrative analysis of genomic and transcriptomic alterations of AGR2 and AGR3 in cancer.
Fessart D, Villamor I, Chevet E, Delom F, Robert J
Open biology ; 2022 Jul 01
The Anterior GRadient (AGR) family proteins in epithelial ovarian cancer.
Fessart D, Robert J, Hartog C, Chevet E, Delom F, Babin G
Journal of experimental & clinical cancer research : CR ; 2021 Aug 27

POETIC Platform
Project members

Protein Maturation by PCSKs and Onco-Immunology

PCSK family consists of 7 members, namely, furin, PC1, PC2, PC4, PACE4, PC5 and PC7 that convert their unprocessed substrates into functional molecules by cleaving their basic amino acid motifs (K/R)-(X)n-(K/R)↓, where n is 0, 2, 4, or 6 and X is any amino acid. These enzymes play an influential role in maintaining homeostasis but also are involved in various pathological conditions. Various PCSKs activate proteins involved in malignant transformation and progression including cell surface-expressed receptors (e.g., integrins, matrix metalloproteinases (MMPs), and growth factors and receptor required for tumor angiogenesis, including VEGF-C and IGF-1 Receptor.

Recently, we revealed the first direct evidence for the critical importance of PCSK activity in the regulation of the immune checkpoint inhibitors, particularly PD-1 on T cells and their importance in TILs infiltration in developed tumors.

In the current project using various in vitro and in vivo assays we will characterize the importance of PCSK in immune checkpoints, and tumorigenesis. The results that will be obtained will shed more light on how blocking PCSK activity and signaling might open doors to a new class of anti-tumorigenic and immune checkpoints regulators.

Project members
Noteworthy publications
Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer.
Tomé M, Pappalardo A, Soulet F, López JJ, Olaizola J, Leger Y, Dubreuil M, Mouchard A, Fessart D, Delom F, Pitard V, Bechade D, Fonck M, Rosado JA, Ghiringhelli F, Déchanet-Merville J, Soubeyran I, Siegfried G, Evrard S, Khatib AM
Cancer research ; 2019 Oct 01
Loss of the proprotein convertase Furin in T cells represses mammary tumorigenesis in oncogene-driven triple negative breast cancer.
He Z, Khatib AM, Creemers JWM
Cancer letters ; 2020 Aug 01

News

Events

Jobs offers

Team’s noteworthy publications

Modulation of Protein Disulfide Isomerase Functions by Localization: The Example of the Anterior Gradient Family.
Pierre AS, Gavriel N, Guilbard M, Ogier-Denis E, Chevet E, Delom F, Igbaria A
Antioxidants & redox signaling ; 2024 Oct 01
Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer.
Tomé M, Pappalardo A, Soulet F, López JJ, Olaizola J, Leger Y, Dubreuil M, Mouchard A, Fessart D, Delom F, Pitard V, Bechade D, Fonck M, Rosado JA, Ghiringhelli F, Déchanet-Merville J, Soubeyran I, Siegfried G, Evrard S, Khatib AM
Cancer research ; 2019 Oct 01
The Anterior GRadient (AGR) family proteins in epithelial ovarian cancer.
Fessart D, Robert J, Hartog C, Chevet E, Delom F, Babin G
Journal of experimental & clinical cancer research : CR ; 2021 Aug 27
AGR2 protein expression in colorectal tumour epithelialcompartment.
Chevet E, Bassal F, Beq S, Bonhomme B, Boisteau E, Calloch J, Cazals-Hatem D, Delom F, Fessart D, Evrard S, Hrstka R, Hupp T, Lièvre A, Louis E, Mariau J, Meuwis MA, Ogier-Denis E, Paradis V, Pernot S, Pineau R, Treton X, Velasco V, Vieujean S
Gut ; 2022 Dec 09
Integrative analysis of genomic and transcriptomic alterations of AGR2 and AGR3 in cancer.
Fessart D, Villamor I, Chevet E, Delom F, Robert J
Open biology ; 2022 Jul 01

Partners

Team leaders

A.Majid KHATIB
Research Director / DR

Frederic DELOM
Lecturer / MCU

Team members

Guillaume BABIN
Clinician / PH

Wendy COMANDATORE
Technician / Tech

Frederic DELOM
Lecturer / MCU

Sandrine FEDOU
Engineer Assistant / AI


Researcher / CR

Léna GOSSET
Technician / Tech

Marianne GUILBARD
PhD Student / Doc

Frédéric GUYON
Clinician / PH

A.Majid KHATIB
Research Director / DR

Coriolan LEBRETON
Clinician / PH

Jacques ROBERT
Professor Emeritus / PU émérite

Saïd TAOUJI
Engineer / IE