Abstract
Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment over the past decade. However, although the immune landscape suggests a strong rationale for the use of these agents in patients with head and neck squamous cell carcinoma, the available clinical evidence indicates that most patients currently do not respond to ICI monotherapy. Radiotherapy is a primary treatment modality for many patients with locally advanced head and neck cancer. While ionizing radiation traditionally has been thought to act in a purely cytotoxic fashion, a growing body of preclinical studies have demonstrated additional profound immunomodulatory effects. Consequently, there has been a surge of interest in the potential synergy between radiotherapy and immunotherapy, both the potential for radiotherapy to augment the systemic anti-tumor immune response and the potential for immunotherapy to improve in-field tumor response to radiation. In this review, we summarize the current preclinical and clinical evidence for radioimmunotherapy, with a particular focus on studies directly relevant to head and neck squamous cell carcinoma, as well as existing challenges and future directions for this emerging field.
Highlights
Head and neck cancers comprise a significant portion of the global cancer burden; when aggregating subsites, they are the 8th most common cancer worldwide by both incidence and mortality [1]
When combined with traditional chemoradiation, addition of these two agents increased the CD8+ T-cell/T-regulatory cells (Tregs) ratio and decreased immunosuppression [44]. In this particular model system the combination of radiation with PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition only minimally altered the immunologically cold tumor microenvironment, but the addition of cyclophosphamide and the inducible nitric oxide synthase (iNOS) inhibitor shifted the balance of infiltrated immune cells away from immunosuppressive types to those more associated with anti-tumor immunity
No prospective clinical data has yet been published on the combination of radiation and Immune checkpoint inhibitors (ICI) in patients with oligometastatic HNSCC, though there is at least one ongoing clinical trial (NCT03283605, which examines the use of durvalumab, tremelimumab [a CTLA-4 inhibitor], and stereotactic body radiotherapy (SBRT) in patients with HNSCC with fewer than 10 metastases)
Summary
Head and Neck Cancer: Current Evidence and Challenges. Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment over the past decade. The immune landscape suggests a strong rationale for the use of these agents in patients with head and neck squamous cell carcinoma, the available clinical evidence indicates that most patients currently do not respond to ICI monotherapy. There has been a surge of interest in the potential synergy between radiotherapy and immunotherapy, both the potential for radiotherapy to augment the systemic anti-tumor immune response and the potential for immunotherapy to improve in-field tumor response to radiation. We summarize the current preclinical and clinical evidence for radioimmunotherapy, with a particular focus on studies directly relevant to head and neck squamous cell carcinoma, as well as existing challenges and future directions for this emerging field
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