Centre of expertise for research in immuno-oncology and transplantation
Tumoral escape

Theme based on oncology:
immunoresistance, chemoresistance and tumoral radioresistance

This area aims to bring together the teams working on onco-immunology, oncogenicity and nuclear oncology in order to tackle, in a crossed manner, the possible links between tumor resistance to :

  • immunotherapies (immunoresistance)
  • chemotherapies (chemoresistance)
  • ionising radiations (tumour radioresistance)

Accepting the challenge of personalised medicine, our teams are working to develop targeted therapies adapted to the tumour’s biological specifics and identifying new therapeutic targets in:

  • haematology (MM, mantle-cell lymphoma, acute myeloid leukemia (AML), GvH)
  • onco-dermatology (melanoma)
  • digestive oncology (colorectal cancers (CRC)

These themes are tackled in close cooperation with the immuno-transplantation pole via the  LabEX IGO and the IHU CESTI , thus making possible :

  • to study both antitumour and allospecific immunity
  • to assess the relationship between tumour immune escape mechanisms and operational tolerance
  • to assess the transplantation immunosuppressor potential of antitumour therapeutic strategies.

This area is structured around 2 main themes and features 6 transversal objectives :

Theme 4. Carcinogenetic and tumour progression mechanisms in oncohaematology, oncodermatology and digestive oncology. Diagnostic and therapeutic implications

  • Aim 4.1. Tumour profiling of apoptosis effectors  (MM, melanoma).
    -Quantification and functional evaluation of proteins from the Bcl2 family, particularly using type BH3 profiling systematic approaches
    -Study of the interrelations between these effectors, of mitochondrial metabolism regulation and oxydative stress dependant on and independent of p53.
    -Development of in vivo monitoring approaches for cell death in response to targeted therapies.
    -Evaluation of the predictive value of these apoptosis effectors in tumour response to chemotherapy.
  • Aim 4.2. Molecular and protein profiling of tumours resistant to treatment (MM, mantel cell lymphoma, acute myeloblastic leukaemia). 
    – To characterise clonal evolution and development approaches that enable monitoring of this evolution during escape from treatment.
    – To study the deregulation of splicing programs during tumour progression.
    – To assess the predictive value of identified markers and their implication for diagnosis and treatment with a view to a personalised therapeutic strategy.
  • Aim 4.3. Monitoring circulating tumour cells (CRC, melanoma).
    – Assessment of the diagnostic and prognostic value of the CTC frequency estimated by proven approaches (such as Veridex CellSearch).
    – Development of new CTC enriching and monitoring approaches using multiparameter cytometry .

Theme 5. Antitumour immunity and development of immunotherapies in oncohaematology and oncodermatology

  • Aim 5.1. Antitumour immunosurveillance and immune escape (melanoma, transplantation).
    – Assessment of the effectors of antitumour cellular immunity and of the tumour escape mechanisms in vitro and in preclinical models in vivo (humanised and/or xenotransplated mice).
    –  Assessment of possible parallels between tumour escape, allogeneic tolerance and resistance to immuno, chemo and radioinduced apoptosis.
  • Aim 5.2. Immunomonitoring (melanoma, MM, CRC, transplantation). 
    – Coordinated preparation in the CHU’s (immunotransplantation) and the SFR’s (immuno-oncology) two immunomonitoring platforms of standardised in-depth monitoring protocols for inane and adaptive effectors in treatment-naive cancer patients or those receiving immunotherapy.
    – Preparation of new radiomarking and monitoring approaches in vivo for injected immunitary cells.
    – Preparation of new monitoring approaches for cell death in vivo .
  • Aim 5.3. Immunotherapy (melanoma, MM, GvH, lymphomas B, CRC, transplantation).
    –  Development of clinical grade protocols for the filtering, expansion and differentiation of lymphocytes T and dendritic cells for adoptive transfer purposes.
    – Assessment of peptide or viral therapy vaccination strategies, alone or in combination with immunoadjuvant or immunodepletive approaches targeting suppressive populations or immunogen radio or chemotherapies .

 

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