Prospective trials should (i) define the duration of the interferon window; (ii) test varying mRNA doses and formulations; and (iii) prespecify biomarkers—plasma IFN-α peaks, transient myeloid PD-L1 induction, and short-term increases in the tumor PD-L1 TPS—to trigger ICI administration. The gene discussed is IFNA1; the disease is neoplasm.