HSP70 - EXOSOMES IN CANCER THERANOSTICS

Orateur : Carmen GARRIDO (University of Burgundy, Dijon)

Exosomes are extracellular vesicles ( 50–200 nm) released into the extracellular environment via the endosomal vesicle pathway by fusion with the plasma membrane. We have demonstrated that cancer cells, but not “normal” cells, release exosomes expressing the heat shock protein-70 (HSP70) in their membrane. This extracellular HSP70 through its association to the toll-receptor 2 on myeloid-derived suppressive cells can block the development of an efficient anticancer immune response (Chalmin et al JCI 2010 ; Arlet, Nature 2014 ; Gobbo et al, JNCI 2016 ; Busdesco et al, Blood 2018). Therefore, the inhibition of HSP70-exosomes is an interesting strategy in cancer therapy. Since one single cancer cell can release thousands of HSP70-exosomes, detection of those cancerderived exosomes should be an important step toward early cancer detection. To capture HSP70- exosomes from human fluids, we have set up an innovative interference biolayer approach using as a high affinity ligand a HSP70 peptide aptamer that we have selected by its ability to specifically bind the extracellular domain of membrane-bound HSP70 (Patents 2016-8). We have opened a 3-years prospective study called ExoDiag with the anticancer center Georges François Leclerc (inclusion of patients started in 2016). ExoDiag will include 60 patients with newly diagnosed cancer (n=15 nonmetastatic breast ; n=15 metastatic breast, n=20 metastatic lung and n=10 metastatic ovary) and 20 controls. Results analyzed so far indicated that 1) HSP70-exosomes are markers of tumor dissemination : their level is very high in metastatic patients compared to patients with primary tumors or healthy volunteers ; 2) HSP70-exosomes are detected much earlier than circulating tumor cells (determined by CellSearch) ; 3) there seems to be a cancer-type specific miRNA (small non-coding RNAs) signature in these circulating HSP70-exosomes that can inform us the cellular origin of the HSP70-exosome and thereby of the metastasis. These results will be translated in an earlier and adapted care and management of the patient.

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