Immunology and oncogenesis of lymphoid tumours

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Research topics & objectives

The team’s objectives are to: describe and understand the oncogenic alterations implicated in the transformation of normal lymphocytes into lymphoma cells in order to improve the diagnostic and therapeutic care of patients suffering from lymphomas; understand the mechanisms responsible for the decrease in anti-cancer T-cell responses linked to the expression of the immunosuppressive enzyme IL4I1.

Research topics

  • Oncogenesis of T-cell lymphomas
  • Identification of diagnostic biomarkers, lymphoma prognostics and theranostics
  • Immunoregulation with the enzyme IL4I1

Lymphoma sub-types

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

Key words

Peripheral T-cell lymphomas, Oncogenesis, IL4I1, Biomarkers

PhilippeGaulardRechercheLymphome
Philippe Gaulard Manager - Créteil
Lymphomes B Diffus à grandes cellules
Expertise

Expertise

BIOLOGICAL TARGETS AND IN VITRO/IN VIVO/EX VIVO MODELS

Targets

  • Alterations in the epigenetic regulators and in cell signalling (particularly in the TCR and co-stimulation molecule pathway) in T-cell lymphomas
  • Immunomodulatory effect of the enzyme IL4I1
  • Target study on tumour lymphoid lineages (B and T cells)
  • TET2, c-MYC, IDO, IL4I1

Models

  • Mouse KO IL4I1, double KO IL4I1/IDO
  • Many lymphoid lineages (B and T cells)
  • Transgenic mouse model P14 (TCR antigp33)

BLOOD AND TISSUE BIOMARKERS

  • Identification of somatic mutations: targeted sequencing or not (Sanger, PCR all spé, NGS, HRM), allelic discrimination
  • Genetic tissue expression profile: RT-PCR, micro-arrays, RT-MLPA
  • Identification of quantitative or structural genetic alterations (FISH, a CGH)
  • Protein analysis in situ: immunohistochemistry for the expression of tumour markers and markers of the immune microenvironment, of which IL4I1 (monoclonal antibody developed by the team)
  • Tracking T or NK lymphoid populations (blood) and the residual disease (blood, marrow) (during treatment)

TOOLS, PROCESSES AND PLATFORMS LINKED TO THE CLINICAL RESEARCH

Biological resources/collections:

  • TENOMIC collection of more than 900 T-cell lymphomas, annotated with molecular data
  • Collections of cutaneous lymphomas (KIRs, CELLUCUT and LYCUT)
  • Collections GHEDI, MALT…
  • The Mondor biological resource platform

Imaging platform(immunohistochemistry, FISH, TMAs, virtual slides and image analysis linked to the LYSA-P platform).

Clinical resources:

  • -LYSA trials
  • CLIP2 (early phase clinical trial centre with the INCa label), for the development of early trials

INNOVATING TECHNOLOGY

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

Platforms & technical resources

  • Imaging platform (immunohistochemistry, FISH, TMAs, virtual slides and image analysis linked to the LYSA-P platform)
  • Microscopy
  • FISH
  • Tissue micro-arrays
  • Virtual images
  • NGS genomic platform…

R&D offer

  • In vitro pre-clinical models
  • Access to annotated and well-characterised lymphoma collections (more than 800 T-cell lymphomas in the collection TECNOMIC)
  • Histopathology, immunohistochemistry, FISH, molecular diagnostic, immunomonitoring
  • Early clinical trials