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 .