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

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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

RNAEXplore

RNAExplore – Spatial Transcriptomics Platform

RNAExplore is a technical platform dedicated to spatial transcriptomics, enabling the characterization of RNA expression while preserving its spatial and cellular context within tissues. This approach provides high-resolution mapping of cell populations, molecular signatures, and cellular interactions within the tissue microenvironment.

RNAEXplore supports research projects from experimental design to data acquisition and analysis, with applications in cancer research, neuroscience, immunology, and vascular biology.

Project members

XenoFish Platform

XenoFish Platform

The XenoFish platform specializes in the use of the zebrafish model (Danio rerio) for in vivo studies of physiological and pathological mechanisms, as well as for the evaluation of novel therapeutic approaches. Owing to its natural transparency and rapid development, the zebrafish enables real-time visualization, monitoring, and quantification of a wide range of biological processes.

XenoFish supports research projects from experimental design through to data analysis and interpretation. The platform provides recognized expertise across multiple application areas, including cancer research, angiogenesis, inflammation, toxicology, and the preclinical assessment of therapeutic compounds.

Project members

News

M. Khatib – team 2 – Horizon Europe project – Focus 4R

Open Day: The general public at the heart of digestive cancer research

The XenoFish platform hosts a workshop for high-school students at a scientific symposium

Interview Pr. Jacques Robert – Cancer: warning of a “tsunami” of false information

SFC 2023 Training “Tumor heterogeneity: from DNA sequencing to clinical applications”

Events

13/07/2026 • thesis defense Chloé Porcheron, team 2.1

09/07/2026 • ChemBioNA2026: 2026 Chemistry and Biology Conference in Nouvelle-Aquitaine

25/06/2026 • Thesis Defense by Mathieu Bourgeais, Team 2 BRIC & CBMN

22/06/2026 • Invited seminar – Cédric Chaveroux – 22-06-2026

13/04/2026 • Thesis Defense Yiyang LIU, team 2 RyTme

10/03/2026 • Thesis defense Marianne Guilbard

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