Previous studies have reported that Siglec-15 expression is mutually exclusive to B7-H1 (PD-L1) in TME of several cancer types, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), breast and bladder cancers (13, 17), indicating that Siglec-15 works independently from the PD-L1/PD-1 pathway to restrain antitumor immune responses. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.