Our comprehensive irGEP indicated that tumor tissue in CUP patients expresses the targets of such novel ICIs including LAG-3, TIM-3, CD73, B7-H3, and transforming growth factor–β (TGF-β) as well as those of conventional ICIs including PD-L1, PD-L2, PD-1, and cytotoxic T lymphocyte antigen–4 (CTLA-4). Here, LAG3 is linked to neoplasm.