Immune checkpoint inhibitors (ICIs) have been approved for use in multiple tumor types and subsequently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, influencing real-world clinical management of patients with cancer.1 Despite this, only an estimated 12.5% of eligible (based on PD-L1 positivity) patients are reported to respond to ICI,2 while frequent immune-related adverse events are observed in ICI treated patients.3,4 Hence, it is of the utmost importance to further develop both positive and negative predictive biomarkers for ICI response. The gene discussed is CD274; the disease is neoplasm.