We created a quadruple humanized mouse model expressing NKG2A, CD94, PD-1, and PD-L1 to investigate potential combination therapies. Flow cytometry confirmed expression of these targets on immune cells. In vivo testing with antibodies targeting NKG2A and PD-L1 showed that combination therapy significantly reduced tumor growth compared to NKG2A single antibody treatment. These findings validate the humanized mouse model for further evaluation of combination therapies.