Experimental Histopathology ICEP
Emilie Agavnian
Technician
Lorène Ferreira
Technician
Marion Rubis
Assistant-Ingineer
Muge Kaya
Hospital practitioner
Nils Collinet
Engineer
Located at the interface between the Institut Paoli-Calmettes (IPC) and the Centre de Recherche en Cancérologie de Marseille (CRCM), ICEP provides support and expertise for the histological aspects of clinical, translational and fundamental research projects on the site. ICEP also provides services for academic and industrial partners.
The ICEP platform offers histotechnology services such as the manufacture of blocks and Microarray Tissues, sectioning of frozen and/or formalin-fixed and paraffin-embedded samples, histological staining and immunostaining, slide digitization, image analysis and anatomopathological analysis.
ICEP is also dedicated to developing innovative space multiplex technologies. ICEP is the "cancer pilot site" for Miltenyi's MACSima technology. This automated system, dedicated to proteomic multiplex technology, can measure several dozen markers simultaneously on a sample. This enables precise mapping of the tumor, immune infiltrate and microenvironment cells with single-cell resolution.
Visium HD and Xenium spatial transcriptomics multiplex technologies from 10X Genomics are currently being deployed. These technologies, which enable the profiling of 300 to 5000 genes at sub-cellular resolution, are a revolutionary tool for characterizing the different cell types in a tissue, signaling pathways and cell-cell interactions.
This equipment is part of translational and clinical research projects (therapeutic decision support). They are aimed at discovering new therapeutic targets and biomarkers for diagnosis, and are revolutionizing our understanding of tumor genesis and progression, as well as the response of each cancer to treatment.
Equipment
- Cryostat, Microm NX70: Device for producing thin sections of frozen tissue.
- Microtome, Leica RM2235: Used for fine cutting of fixed, paraffin-embedded tissue.
- Microtome, Microm HM340E with Niagara system: A device for making thin sections of precious samples of any size, fixed and embedded in kerosene, while preserving the biological material as far as possible.
- Vibratome, Leica VT 1200S: Precision tissue cutter without freezing or embedding.
- Tissue Arrayer, Excilone Minicore 3: Equipment for including several hundred biopsies from different donor blocks in a single kerosene block.
- Immunohistochemistry Automat, Roche Discovery Ultra: Automate for single or multi-labeling immunohistochemical (IHC) and immunofluorescent (IF) staining.
- Microscopes, Nikon Eclipse Ci: High-magnification optical instruments for observing microscopic elements in white light.
- Microscope 2 heads, Leica DMLB2: High-magnification optical instrument for observing microscopic elements in white light with two observers.
- Fluorescence microscope, Leica DMRXA: High-magnification optical instrument for observing microscopic elements in fluorescence.
- Camera, Nikon MBA95000: Allows multiple users to view and capture histological slides observed under the microscope.
- Slide scanner, Hamamatsu Nanozoomer 2.0 HT: Enables brightfield scanning of histological slides. Capacity: 210 slides. Scans entire slides at X20 or X40 magnification.
- Slide scanner, Hamamatsu S60 V2 fluo: Enables brightfield and fluorescence scanning of histological slides. Possibility of scanning mega-slides. Capacity for 60 standard slides or 30 mega-slides. Whole slide scans at X20 or X40 magnification.
- Prep Station, Nanostring Ncounter Dx: Prepares samples for multi-gene expression assays.
- Digital analyzer, Nanostring Ncounter Flex: Measures the expression of several hundred genes in a single sample.
- Spatial Proteomics Multiplex technology, MACSima Miltenyi: Enables several dozen to hundreds of proteins to be tagged on a single FFPE or FF sample.
- Transcriptome probe transfer technology, Visium Cyt'Assist (10x Genomics): Instrument facilitating the transfer of transcriptome probes from standard glass slides to Visium slides, for full transcriptome spatial profiling with cellular resolution on tissue section from FFPE and/or FF samples.
- Multiplex Spatial Transcriptomics technology, Xenium (10x Genomics): Technology for transcriptomic profiling (up to 5000 genes) at sub-cellular resolution.
- Image analysis software, Calopix Research (Tribun): Calopix lets you view, annotate and share virtual slides. This software can also be used for quantification using various algorithms, as well as machine learning, and is an invaluable aid in the identification and analysis of TMA spots.
- Image analysis software, MACSiQ Miltenyi: MACSiQ enables you to visualize, quantify and analyze the expression of several dozen or even hundreds of proteins from a single sample (3 licenses, 2 of which are available by reservation).
- Image viewing license, NDP View2 (Hamamatsu): Tool for viewing digitized slides in brightfield or fluorescence.
- Alignment and visualization software, Loupe browser (10x Genomics): Tool for aligning images from Cyt'Assist, a high-resolution slide scanner and sequencing data from Visium SD and HD technologies.
- Analysis software, Space ranger (10x Genomics): A tool that brings together a set of analysis pipelines that process Visium data with brightfield or fluorescence microscope images, enabling users to map the entire transcriptome in a variety of tissues.
- Visualization and analysis software, Xenium Explorer (10x Genomics): Data visualization tool based on Xenium technology. Xenium Explorer lets you visualize transcript localization at cellular or even sub-cellular resolution, and perform segmentation.
Examples of projects
PROJECT OFFICER
Marc Lopez
PROJECT OFFICER
Daniel Olive
Project members :
Anne FarinaEngineer
Marion RubisEngineer
Muge KayaHospital practitioner
Emmanuelle CharafeResearch Hospital Practitioner
Histological validation of an antibody-drug conjugate in breast cancer
The ICEP platform played an active role in the development of a new ADC therapeutic antibody. The target and the antibody were developed at CRCM and led to the founding of the biotech Emergence Therapeutics, as well as the setting up of a Phase I clinical trial in March 2024 in the USA and early 2025 in France, notably at the IPC site.
Project members :
Nils CollinetEngineer
Marion RubisEngineer
Lorène FerreiraTechnician
Anne FarinaEngineer
Michel Aurrand-LionsResearcher
Spatial Transcriptomics" Structuring Action (ST)
The aim of the Spatial Transcriptomics Structuring Action is to facilitate the deployment in Nice/Sophia Antipolis and Marseille of the cutting-edge equipment required for ST analysis, and to set up a working group of histogenomic researchers and engineers and bioinformaticians specialized in all stages from the production to the analysis and validation of single-cell and ST data, advance knowledge of tumor cell diversity and immune infiltration for two major types of cancer, develop methods for spatial analysis of the adaptive immune receptor repertoire (AIRR), and provide training and analysis/exploration software solutions to enable the Cancéropôle PACA community to rapidly acquire the essential know-how in this field.
Project members :
Marion RubisEngineer
Emilie AgavnianTechnician
Flora PoizatResearcher
GEMPRED-RETRO-IPC 2021-070
Description: Identification of a molecular signature of response to Gemcitabine in patients with metastatic pancreatic adenocarcinoma. This project applied the GemCore signature to the non-comparative Phase IV study evaluating the efficacy of first-line gemcitabine chemotherapy in patients with GemCore+ metastatic pancreatic adenocarcinoma who were not candidates for FOLFIRINOX.
Project members :
Nils CollinetEngineer
Marion RubisEngineer
Lorène FerreiraTechnician
Anne FarinaEngineer
Emilie AgavnianTechnician
Spatial organization of the bone marrow microenvironment in myeloid hemopathies (OS3M-IPC 2024-026)
The prognosis of myelodysplastic syndromes (MDS) has long been based on the measurement of the R-IPSS score, which takes into account cytopenia, cytogenetic alterations and the quantity of blasts in the OM at diagnosis. Since the publication of a molecular score in 2022 (IPSS-M), patient stratification has been greatly refined. The IPSS-M has been validated in several studies and represents a significant advance in the selection of patients eligible for transplantation. Nevertheless, it does not predict response in patients treated with hypomethylating agents, suggesting that microenvironmental factors may also play a role in the progression of MDS to acute myeloid leukemia. There is therefore a pressing need to identify alterations in the bone marrow microenvironment that could better predict disease progression. This question is addressed in this project by combining proteomics and spatial transcriptomics studies on histological sections of bone tissue.
Education and Training
- Internal user training.
- Teaching in Bachelor's 1 Pro BIBBI, Master's 1 and 2 Biology Health - Health Technology Course.
- Supervision/Training/internships: BTS, Master 1 and 2, thesis students.
Featured Publications
11/2024
Marc Lopez, Emerence Crompot, Emmanuelle Josselin, Anne Farina, Marion Rubis, Remy Castellano, Joanna Fares, Maria Wehbe, Yves Collette, Emmanuelle Charafe, Stéphanie Blanchin, François Romagne, Anikó Pálfi, Torsten Hechler, Andreas Pahl, Hatem A Azim Jr, Florence Lhospice, Emilie Mamessier, François Bertucci, Jack Elands, Xavier Préville, and Daniel Olive.
04/2023
Adrienne Anginot, Julie Nguyen, Zeina Abou Nader, Vincent Rondeau, Amélie Bonaud, Maria Kalogeraki, Antoine Boutin, Julia P Lemos, Valeria Bisio, Joyce Koenen , Lea Hanna Doumit Sakr, Amandine Picart, Amélie Coudert, Sylvain Provot, Nicolas Dulphy, Michel Aurrand-Lions, Stéphane J C Mancini, Gwendal Lazennec, David H McDermott, Fabien Guidez, Claudine Blin-Wakkach, Philip M Murphy, Martine Cohen-Solal, Marion Espéli, Matthieu Rouleau, Karl Balabanian.
05/2020
Richart L, Picod-Chedotel ML, Wassef M, Macario M, Aflaki S, Salvador MA, Héry T, Dauphin A, Wicinski J, Chevrier V, Pastor S, Guittard G, Le Cam S, Kamhawi H, Castellano R, Guasch G, Charafe-Jauffret E, Heard E, Margueron R, Ginestier C.
04/2021
Fayad R, Rojas MV, Partisani M, Finetti P , Dib S, Abelanet S, Virolle V, Farina A, Cabaud O, Lopez M, Birnbaum D, Bertucci F, Franco M, Luton F.
04/2017
M-Rabet M, Cabaud O, Josselin E, Finetti P , Castellano R, Farina A, Agavnian-Couquiaud E, Saviane G, Collette Y, Viens P , Gonçalves A, Ginestier C, Charafe-Jauffret E, Birnbaum D, Olive D, Bertucci F, Lopez M.
