Fig. 5From: Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinomaTME modulation by cetuximab and nivolumab and the potential breakthrough treatment strategy using ipilimumab for HPD. Inhibiting EGFR modulates the tumor immune microenvironment in several ways, including enhancing MHC class I and II expression, decreasing the suppressive function of Tregs, promoting CTL activity, and reducing T cell apoptosis. PD-1 blockade may facilitate the proliferation of highly suppressive PD-1 + effector Treg cells in HPDs, resulting in the inhibition of antitumor immunity. Highly activated tumor-infiltrating PD-1 + effector Treg cells show higher CTLA-4 expression levels than PD-1- effector Treg cells. As the PD-1 blockade significantly enhances Treg cell suppressive activity, PD-1 blockade facilitates the proliferation of highly suppressive PD-1 + effector Treg cells expressing high CTLA-4 in HPDs, resulting in immunosuppression in HNSCC. Moreover, cetuximab treatment increases the FoxP3 + intratumoral effector Tregs expressing CTLA-4, suggesting the combination with ipilimumab restores the cytolytic functions of NK cells mediating ADCC. Targeting CTLA-4 high PD-1 effector Tregs for HNSCC may show a high response to the tumor and improve survivalBack to article page