CTLA4 and neoplasm: In HNSCC, the immune system is known to have a pivotal role, as high density of tumor-infiltrating lymphocytes (TILs) is associated with improved outcome of patients (26, 27) while tumor tissues and draining lymph-nodes respectively, present a high density of CTLs expressing PD-1 and regulatory Tregs over-expressing CTLA-4; a finding that clearly suggests a high suppressive activity of either peripheral and central immune-checkpoints in these patients (28).