Preclinical studies have demonstrated that blockade of CTLA-4 upregulates ICOS on CD4+ T cells, prompting the ongoing Phase II clinical trial of the ICOS agonist vopratelimab in combination with ipilimumab for PD-1/PD-L1-resistant NSCLC (NCT03989362). The gene discussed is CD274; the disease is non-small cell lung carcinoma.