Immune modulation of head and neck squamous cell carcinoma and the tumor microenvironment by conventional therapeutics

Head and neck squamous cell carcinoma (HNSCC) accounts for more than 600,000 cases and 380,000 deaths annually worldwide. While human papilloma virus (HPV)-associated HNSCCs have better overall survival compared to HPV-negative HNSCC, loco-regional recurrence remains a significant cause of mortality and additional combinatorial strategies are needed to improve outcomes. The primary conventional therapies to treat HNSCC are surgery, radiation, and chemotherapies; however multiple other targeted systemic options are used and being tested including cetuximab, bevacizumab, mTOR inhibitors, and metformin. In 2016 the first checkpoint blockade immunotherapy was approved for recurrent or metastatic HNSCC refractory to platinum based chemotherapy. This immunotherapy approval confirmed the critical importance of the immune system and immuno-modulation in HNSCC pathogenesis, response to treatment, and disease control. However, while immuno-oncology agents are rapidly expanding, the role that the immune system plays in the mechanism of action and clinical efficacy of standard conventional therapies is likely underappreciated. In this article, we focus on how conventional and targeted therapies may directly modulate the immune system and the tumor microenvironment to better understand the effects and combinatorial potential of these therapies in the context and era of immunotherapy.

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