Discovered in the 20th century, CTLA‐4 and PD‐1 are the most well‐known targets used in immunotherapies.[5, 6, 7, 8, 9] Several surface molecules, such as TIGIT, GITR, and LAG‐3, have also been recently found to play special roles in the anti‐tumor immune response and can be used as novel targets (Figure 1).[10, 11, 12, 13] The inhibition or activation of these molecules has been demonstrated to exert significant effects on some tumors. The gene discussed is TNFRSF18; the disease is neoplasm.