5.3A2aR mAb combined with TIGIT mAb
The frequency of TIGIT+NK cells in patients’ blood was negatively related to the prognosis of AML. Compared with healthy subjects, AML patients had abnormal NK cell populations in peripheral blood (PB) and bone marrow (BM), which were shown as increased frequency of TIGIT+, PVRIG+, CD39+ and CD69+NK cells. This makes TIGIT a target for AML treatment[38]. Purinergic pathway also regulate the function of NK cells. Proliferation and hypoxia of tumor cells increase the utilization of ATP and activate cancer-related CD39 and CD73, which catalyze the continuous dephosphorylation of ATP to AMP and then to eADO. Extracellular adenosine accumulation interacts with adenosine receptors expressed on the surface of NK cells and inhibits signaling through A2aR, so A2aR antibodies are also an important target for tumor therapy[51]. It has been demonstrated that combined blocking of TIGIT and A2aR could enhance NK-92 cell-mediated cytotoxicity in AML[38]. In other tumors, the combination of TIGIT mAb and A2aR mAb is still being explored[51].