Mary Poupot
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Project: Targeting of pro-tumoral Nurse Like cells in chronic lymphocytic leukemia.
In solid cancer, tumor associated macrophages (TAM) promote tumor development but this role is so far not demonstrated in leukemia. Based on their phenotype (CD163+, CD68+) and transcriptomic profile, we recently showed that Nurse Like Cells (NLC) are TAM in Chronic Lymphocytic Leukemia (CLL). NLC are protecting CLL cells from spontaneous apoptosis and from some chemotherapeutic drugs. Moreover, from a study on lymph nodes from CLL patients, we showed the NLC cell counts in lymph nodes correlates with disease progression. Furthermore, these NLC present a close interaction with proliferating CLL cells. We found that soluble CD163 (sCD163) shed from NLC correlates with bad prognostic, high CD163 level is associated with shorter treatment free survival and overall survival. So, NLC constitute a good target to improve CLL chemotherapies or to propose new therapeutic strategies for this disease.
The project aims at directly targeting NLC in CLL by newly developed antibodies or targeting of CLL / NLC interactions.
In solid cancer, tumor associated macrophages (TAM) promote tumor development but this role is so far not demonstrated in leukemia. Based on their phenotype (CD163+, CD68+) and transcriptomic profile, we recently showed that Nurse Like Cells (NLC) are TAM in Chronic Lymphocytic Leukemia (CLL). NLC are protecting CLL cells from spontaneous apoptosis and from some chemotherapeutic drugs. Moreover, from a study on lymph nodes from CLL patients, we showed the NLC cell counts in lymph nodes correlates with disease progression. Furthermore, these NLC present a close interaction with proliferating CLL cells. We found that soluble CD163 (sCD163) shed from NLC correlates with bad prognostic, high CD163 level is associated with shorter treatment free survival and overall survival. So, NLC constitute a good target to improve CLL chemotherapies or to propose new therapeutic strategies for this disease.
The project aims at directly targeting NLC in CLL by newly developed antibodies or targeting of CLL / NLC interactions.
Animal and Cellular models:
NLC are obtained by an in vitro culture of PBMC (peripheral blood mononuclear cells) isolated from blood sample of CLL patients. They are generated by the differentiation of monocytes through a contact with CLL cells which are present in PBMC of patients.
NLC are obtained by an in vitro culture of PBMC (peripheral blood mononuclear cells) isolated from blood sample of CLL patients. They are generated by the differentiation of monocytes through a contact with CLL cells which are present in PBMC of patients.
Techniques and Methods:
Purification of mononuclear cells from blood sample, culture cell, mice immunization, antibodies production, flow cytometry, confocal microscopy.
Purification of mononuclear cells from blood sample, culture cell, mice immunization, antibodies production, flow cytometry, confocal microscopy.