This argument is even more relevant to the HNSCC setting because metastatic/recurrent cancers often lead to stronger changes in peripheral T cell repertoires.8 This hypothesis was indirectly supported by the recent findings which demonstrated no distinct peripheral immune effects between anti-PD1/CTLA4 single-agent and combination therapy for treating metastatic melanoma.10 The gene discussed is CTLA4; the disease is metastatic melanoma.