Novel Insights of Anti-EGFR Therapy in HNSCC: Combined with Immunotherapy or Not?

Anti-EGFR therapy, especially cetuximab, was validated to induce the innate and adaptive immune responses of HNSCC patients. It is mainly through inducing natural killer (NK) cells mediating antibody-dependent cell-mediated cytotoxicity (ADCC), recruiting multiple tumor-infiltrating immune cells, and finally remodeling the TIME. Moreover, mountains of preclinical models and clinical trials revealed that combining anti-EGFR agents with immunotherapy could enhance the antitumor effectiveness in HNSCC. Anti-EGFR therapy may usher in another dawn in the treatment of patients with HNSCC through combination with immunotherapy. We offer an overview of the ongoing efforts to make out the immunomodulation of the EGFR pathway in both innate and adaptive immune responses; update the constant preclinical models and clinical trials for the combination of anti-EGFR and immunotherapy in HNSCC; and finally evaluate the efficacy and advantages of the combination therapeutic strategies in clinical use.