Although solid, the current assumption that TIGIT inhibition has to rely on PD-1/PD-L1 axis inhibition, on which most clinical trials using anti-TIGIT strategies are based, may be not totally comprehensive; differences could exist between different types of human cancer in relation to the significance of TIGIT expression and its relationship with PD-1/PD-L1, and the relevance of TIGIT expression might have been overlooked, especially in anti-TIGIT monotherapy regimens trials. This evidence concerns the gene CD274 and cancer.