CD274 and cancer: Within the TME, Siglec-15 also contains the same domain composition as the PD-1/B7-H1 immune checkpoint and thereby suppresses immune responses against tumor progression, whereas the activation of suppressed T cells can restore defective immunity through the blockade of PD-1/B7-H1 signaling cascade with monoclonal antibodies which ultimately indicates the evidence of normalization theory in cancer immunotherapy [70, 71].