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PD-1 CPI therapy can generate durable responses with fewer side effects compared to conventional cytotoxic chemotherapy. Unfortunately, CPI can induce an objective response in less than 15 - 20% of non-melanoma solid tumor patients [1-3]. Multiple biomarkers have been evaluated as potential factors predicting response, but none has shown reproducible clinical utility across tumor types. Higher PD-L1 expression in tumor tissue is associated with higher response rates, but a single tumor tissue sample may not reflect spatial and temporal variability in PD-L1 expression. Circulating tumor cells can be collected at multiple timepoints with minimal risk and may provide a more comprehensive and dynamic view of tumor heterogeneity. Higher IRF-1 expression in tumor tissue has been correlated with longer progression-free survival (PFS) in metastatic melanoma patients treated with CPIs [4]. We hypothesize that evaluating both PD-L1 and IRF-1 expression on CTCs may better predict…