CD274 and esophageal squamous cell carcinoma: In the three-armed CheckMate 648 study, which represented also a phase III study, the first-line therapy in unresectable and advanced, recurrent, or metastatic PD-L1-positive squamous cell carcinoma of the esophagus (TPS ≥ 1%; tumor proportion score) resulted, both for therapy with nivolumab in combination with cisplatin and 5-FU (15.4 vs. 9.1 months; HR: 0.54; p < 0.001), as well as for the ICI combination of nivolumab plus ipilimumab alone (13.7 vs. 9.1 months; HR: 0.64; p = 0.001), in a significant advantage in overall survival compared to chemotherapy alone (Doki et al. 2022).