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Immunology and Oncogenesis of Lymphoid Tumors

Leader: Philippe Gaulard

CréteilU955-9 INSERM

Research Areas & Objectives

Research areas

- Oncogenesis of peripheral T-cell lymphomas
- Immunoregulation by the immunosuppressive enzyme IL4I1
- Identification of diagnostic, prognostic and predictive biomarkers in lymphomas

Objectives

The team’s objectives are to:

- describe oncogenic events that transform normal lymphocytes to tumour cells to improve lymphoma diagnosis and treatment,
- understand the mechanisms responsible of the decreased anti-cancer immune responses mediated by IL4I1.

Lymphoma Sub-types

- Peripheral T-cell lymphoma
- B-cell lymphoma (diffuse large B cell lymphoma)

Expertise

Biological targets and in vitro/in vivo/ex vivo models

Targets:
- Molecular alterations in lymphoma entities, especially in epigenetic regulators and in cell signalling (especially TCR and co stimulatory signalling) in T-cell lymphomas
- Immunomodulatory effect of IL4I1
- Target studies on lymphoid tumor cell lines (B and T)
- TET2, c-MYC, IDO, IL4I1

Models :
- KO IL4I1 and double KO IL4I1/IDO mice
- Numerous lymphoma cell lines
- Mouse transgenic model : P14 (TCR antigp33)

Blood and tissue biomarkers

- Identification of somatic mutations: targeted or not sequencing (Sanger, PCR all spe, NGS, HRM), allelic discrimination
- Tissue gene expression profiling: RT-PCR, micro-arrays, RT-MLPA
- Identification of quantitative or structural gene alterations (FISH, a CGH)
- In situ analysis: immunohistochemistry for the expression of tumor and immune microenvironment markers including IL4I1 (monoclonal antibody developed by the group), including multiple labeling, RNAscope, BaseScope
- Monitoring of lymphoid T or NK populations (blood) and residual disease (blood, bone marrow)

Tools, processes and platforms in connection with clinical research

Biological ressources:
- TENOMIC collection: more than 900 T-cell lymphomas annotated with molecular data
- Skin lymphoma collections (KIRs, CELLUCUT et LYCUT)
- GHEDI, MALT collections
- Mondor biobank

Imaging platform (IHC, FISH, TMAs, digital slides and image analysis in connection with LYSA-P platform)

Clinical ressources:
- LYSA trials
- CLIP², allowing development of early phase clinical trial

Innovative Technologies

- NGS (T-cell lymphoma NGS panel)
- RT-MLPA
- a-CGH
- Circulating DNA: liquid biopsy

Platforms & Technical Resources

- Imaging platform (immunohistochemistry, FISH, TMAs,digital slides and image analysis in connection with LYSA-P platform)
- Microscopy
- FISH
- Virtual images
- NGS genomic platform…

R&D Offer

- In vitro preclinical models
- Access to well annotated and characterized lymphoma collection (more than 800 PTCL in TENOMIC)
- Pathological review, immunochemistry, FISH, molecular diagnosis
- Early phase clinical trial

Keywords

Peripheral T cell lymphomas, Oncogenesis, Lymphoma biomarkers; IL4I1

 

Please, download our presentation poster (.pdf)