Within the IMCISION trial, patients who developed a major pathological response (MPR) after neoadjuvant anti-PD-1 monotherapy or concurrent anti-PD-1 and anti-CTLA-4 all remained free of HNSCC at a median follow-up of two years [8], raising the question of whether extensive and potentially mutilating surgery is necessary after a major response to ICB. The gene discussed is CTLA4; the disease is head and neck squamous cell carcinoma.