Immunotherapy in Head and Neck Cancer: Evidence and Perspectives

Abstract

Head and neck squamous cell carcinomas evade immune response through multiple immunologic resistance mechanisms. Two of the most commonly involved checkpoint inhibitory mechanisms are CTLA-4 and PD-1/PD-L1, which act at earlier and later stages of immune response to tumors. Pembrolizumab and nivolumab are PD-1 antibodies that interrupt the immunosuppressive pathway of inhibitory checkpoints, which are used by tumor cells to prevent immune reaction. Both recently gained US FDA approval for the treatment of patients with recurrent or metastatic head and neck cancer with disease progression during or following platinum containing chemotherapy. No conclusions can be drawn on the role of PD-L1 in identifying patients responding to immunotherapy, given that similar studies lead to contrasting results. It will be crucial to identify predictive markers of immunotherapy response, and to evaluate them prospectively. A better understanding of the complex network between tumor, immune system and other oncologic treatments will help us to develop more efficient multimodality treatments.

Integrin αvβ3-targeted radionuclide therapy combined with immune checkpoint blockade immunotherapy synergistically enhances anti-tumor efficacy

“…Therefore, ICB using anti-PD1/PD-L1 mAbs has emerged as a promising treatment strategy in various types of malignancies. Indeed, the PD-1/PD-L1 mAbs pembrolizumab, nivolumab, and atezolizumab have been approved by the United States Food and Drug Administration (FDA) to treat patients with advanced non-small-cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma (HNSCC), and melanoma 6-8.…”

Development and Validation of a Robust Immune Prognostic Signature for Head and Neck Squamous Cell Carcinoma

“…In addition, current treatment strategies often lead to poor clinical outcome and substantial toxicities (8). Therefore, immunotherapy has become a promising therapeutic approach for treating HNSCC (9). Identification of the key immune related genes contributes to a deeper understanding of the molecular mechanisms accounting for HNSCC progression.…”

Targeted Therapy and Traditional Chemotherapy in Melanoma and Cutaneous Squamous Cell Carcinoma

“…8 PD-1 inhibitors, pembrolizumab and nivolumab, have demonstrated improved response rates and improved survival benefit compared with cytotoxic chemotherapy in recurrent or metastatic HNSCC. 9 General toxicities associated with ICIs, termed immune related adverse events (irAEs), include fatigue, rash/pruritis, enterocolitis, arthralgias, hypothyroidism, hepatitis, hypophysitis, pneumonitis, nephritis, and neuritis. [9][10][11] In summary, primary systemic therapies used in HNSCC include platinum-based chemotherapy, anti-EGFR monoclonal antibody, and ICIs.…”

“…9 General toxicities associated with ICIs, termed immune related adverse events (irAEs), include fatigue, rash/pruritis, enterocolitis, arthralgias, hypothyroidism, hepatitis, hypophysitis, pneumonitis, nephritis, and neuritis. [9][10][11] In summary, primary systemic therapies used in HNSCC include platinum-based chemotherapy, anti-EGFR monoclonal antibody, and ICIs. Cisplatin is used in the primary setting, whereas cetuximab, pembrolizumab, and nivolumab are approved for use in the recurrent or metastatic disease setting.…”