The most relevant are mucin domain 3 (TIM3) [49], tackled by the PD-1/TIM3 bispecific antibody RO7121661 [50] and TGF-β, a well known immunosuppressive mediator [51], that is co-inhibited by bintrafusp alfa, an anti-TGF-β/anti-PD-1 agent that showed promising activity in HNSCC [52]; IL-2 [53] and fibroblast-activating protein (FAP) [54] are the targets of RO6874281, a bispecific cytokine acting on tumor-associated fibroblasts, that induced one durable response in one HNSCC patient included in a phase I study [55]. This evidence concerns the gene FAP and head and neck squamous cell carcinoma.