It has been investigated that the CD27 intercellular domain could improve the chimeric antigen receptor targeting trophoblast cell surface antigen 2 (T2-CAR) T cell killing effect via multiple mechanisms (Chen H. et al., 2021) and targeting CD276 might reduce cancer stem cells (CSCs) in neck squamous cell carcinoma (HNSCC) through immune escape (Wang C. et al., 2021). Here, TACSTD2 is linked to head and neck squamous cell carcinoma.