Tumor metastases are responsible for death in the majority of
cancer patients. Here we have explored the role of the ectonucleotidase CD39 in select models of
tumor metastases and further tested the therapeutic anticancer activity of the NTPDase inhibitor
sodium polyoxotungstate (POM-1). CD39 was expressed on
tumor-infiltrating regulatory T cells (Treg), myeloid cells and some NK cells, and it was upregulated on these cells within
tumors early after inoculation in vivo. NK cell numbers and effector functions were increased in globally CD39-deficient mice and also in WT mice treated with POM-1. Dosing with POM-1 suppressed experimental and spontaneous
metastases in four different
tumor models and was well tolerated. This anti-metastatic activity was completely abrogated in mice, that were depleted of NK cells, had IFNγ neutralized or were deficient in CD39 expression in bone marrow-derived cells. POM-1 was highly effective in suppressing
metastases when used in combination with BRAFi/MEKi or anti-PD-1/anti-CTLA-4 or
IL-2. These data highlight the importance of the CD39 pathway in suppressing NK cell-mediated anti-
tumor immunity and validate further the development of CD39-based
therapies in the clinic.