Here, we test a new 4-gene multiplex immunotherapy panel (CD274, PDCD1LG2, CD8A, and IRF1) with research use only (RUO) prototype mRNA expression profile on the GeneXpert closed system using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) for association with clinical benefit after treatment with ICI in metastatic melanoma patients toward the goal of a sensitive and specific test for prediction of benefit from ICI. The gene discussed is IRF1; the disease is metastatic melanoma.