Immune Checkpoint Inhibitors, Small-Molecule Immunotherapies and the Emerging Role of Neutrophil Extracellular Traps in Therapeutic Strategies for Head and Neck Cancer

Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of many cancer types, including head and neck cancers (HNC). When checkpoint and partner proteins bind, these send an “off” signal to T cells, which prevents the immune system from destroying tumor cells. However, in HNC, and indeed many other cancers, more people do not respond and/or suffer from toxic effects than those who do respond. Hence, newer, more effective approaches are needed. The challenge to durable therapy lies in a deeper understanding of the complex interactions between immune cells, tumor cells and the tumor microenvironment. This will help develop therapies that promote lasting tumorlysis by overcoming T-cell exhaustion. Here we explore the strengths and limitations of current ICI therapy in head and neck squamous cell carcinoma (HNSCC). We also review emerging small-molecule immunotherapies and the growing promise of neutrophil extracellular traps in controlling tumor progression and metastasis.

A radiomics model to predict γδ T‐cell abundance and overall survival in head and neck squamous cell carcinoma

“…CTLA-4 is a key regulator of the immune response and inhibits autoreactive T cell activation during the early stages, whereas PD-1 regulates previously activated T cells in the later phases. 38 Tim-3 is associated with immunosuppression in HNSCC. 39 Cytokines and chemokines secreted by tumor cells, stromal cells, and immune cells within the TME influence immune cell recruitment and activation.…”

“…Immune checkpoint molecules are known to regulate immune response. CTLA‐4 is a key regulator of the immune response and inhibits autoreactive T cell activation during the early stages, whereas PD‐1 regulates previously activated T cells in the later phases 38 . Tim‐3 is associated with immunosuppression in HNSCC 39 .…”

Clinical Advances and Future Directions of Oncolytic Virotherapy for Head and Neck Cancer

“…In addition to surgical, radiation, and chemotherapy approaches, targeted therapy, hyperthermia [20], and radioactive particle interstitial brachytherapy [21,22] have been utilized. Immunotherapy [23][24][25] has emerged as a crucial treatment option for HNCs, including immune checkpoint inhibitors (ICIs) [26], antiepidermal growth factor receptor monoclonal antibodies [27], and near-infrared photoimmunotherapy [28,29]. Immunotherapy works by harnessing the patient's own immune system to activate antitumor immune responses, control and eliminate tumor cells, and reverse tumor immune suppression [30].…”