Recent studies highlight the integral role of the interferon gamma receptor pathway in T cell-mediated cytotoxicity against solid but not liquid tumors. IFNγ not only directly facilitates tumor cell death by T cells but also indirectly promotes cytotoxicity via myeloid phagocytosis. Meanwhile, full human ex vivo immune checkpoint drug screening remains challenging. We hypothesized engineered gamma interferon activation site response element luciferase reporter (GAS-Luc2) can be utilized for immune checkpoint drug screening in ex vivo T cell – solid tumor cell coculture systems. We comprehensively profiled cell surface proteins in ATCC’s extensive collection of tumor and immune cell lines, identifying established and novel immune checkpoint molecules and binding ligands. We then engineered GAS-Luc2 reporter tumor cell lines expressing immune checkpoints PD-L1, CD155, and B7-H3/CD276. Luciferase expression was suppressed upon relevant immune checkpoint – ligand engagement. In the presence of an immune checkpoint inhibitor, T cells released IFNγ, activating the JAK-STAT pathway in GAS-Luc2 cells, generating a quantifiable bioluminescent signal for inhibitor evaluation. These reporter lines also detected paracrine IFNγ signaling for immune checkpoint targeted ADCC drug screening. Further development into artificial antigen-presenting cell line (aAPC) significantly enhanced T cell signaling for superior performance in these immune checkpoint drug screening platforms.