EMT-dependent regulation of the ectonucleotidase CD73 in Triple Negative Breast Cancer and its role as a new therapeutic target

Project Details


Cancer immunotherapy made significant advances in recent years due to the introduction of immune checkpoint modulators. However, although some cancer patients display long-lasting clinical responses, the majority remains unresponsive. Triple negative breasts cancer (TNBC) is the most aggressive subtype of breast cancer, with poor therapeutic options and high rates of recurrence and metastasis. Immune checkpoint-based cancer immunotherapy (ICBCI) is still in its infancy in TNBC. PD-1/PD-L1 inhibitors induce modest response rates of 20% in patients with heavily pre-treated, chemotherapy resistant, PD-L1-positive TNBC. This failure is most likely due to tumor adaptation to and evasion from innate and adaptive immunity. Therefore there is an urgent clinical need to specifically target alternative immunosuppressive pathways. Recently, our group reported the involvement of EMT-transcription factors in the positive regulation of PD-L1 and CD47 inhibitory immune checkpoints in breast cancer cells. Very recently, we uncovered a novel EMT-TF-regulated immune checkpoint in TNBC cells: the ectonucleotidase CD73. CD73 is a key inhibitory immune checkpoint via the extra-cellular generation of the immunosuppressive adenosine. CD73 has been recently reported to correlate with a poor prognosis in TNBC. This project aims to understand the EMT-TF-dependent mechanisms of CD73 regulation, and to propose a new and attractive pre-clinical combination therapy based on the simultaneous targeting of EMT and CD73. Such a combination would result in reactivation of anti-tumoral immunity and more potent and durable tumor regression in TNBC.
Effective start/end date15/02/2114/02/23


  • FNRS - Fonds National de la Recherche Scientifique: €186,172.00


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