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Review
. 2019 Jul 15;25(14):4211-4223.
doi: 10.1158/1078-0432.CCR-18-0871. Epub 2019 Feb 27.

Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics

Sayuri Miyauchi  1 , Sangwoo S Kim  1 , John Pang  2 , Kathryn A Gold  3 , J Silvio Gutkind  4 , Joseph A Califano  2   5   6 , Loren K Mell  1 , Ezra E W Cohen  3   6 , Andrew B Sharabi  7   6
Affiliations
Review

Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics

Sayuri Miyauchi et al. Clin Cancer Res. .

Abstract

Head and neck squamous cell carcinoma (HNSCC) accounts for more than 600,000 cases and 380,000 deaths annually worldwide. Although human papillomavirus (HPV)-associated HNSCCs have better overall survival compared with 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 immunomodulation in HNSCC pathogenesis, response to treatment, and disease control. However, although 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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Conflict of interest statement

Conflicts of Interest Statement:

KG reports research funding from Pharmacyclics, Molecular Partners, Pfizer, BerGenBio, Abbvie, and AstraZeneca, and consultant fees from AstraZeneca, Takeda, and Regeneron. J.S.G reports research funding from Kura Oncology and Mavupharma, and consultant fees from Oncoceutics Inc and Vividion Therapeutics. LM reports research funding from Merck and Astrazeneca and consulting fees and honoraria from Merck, Pfizer, and Varian Medical Systems. EC reports research funding from Pfizer, Merck, AstraZeneca, and Bristol-Myers Squibb outside the submitted work. AS reports research funding and honoraria from Pfizer and Varian Medical Systems, consultant fees from Astrazeneca, and other fees from Raysearch and Merck.

Figures

Figure 1.
Figure 1.. Radiation-induced immune responses in head and neck cancer
Radiation induces 1) release of tumor antigens and damage-associated molecular pattern (e.g. HMGB1) via cell death, 2) activation and migration of dendritic cells to lymph node, 3) enhanced cross-presentation of tumor antigens via upregulation of MHC I, and 4) antigen-specific T cell activation and proliferation. Radiation therapy can be combined with immunotherapy (checkpoint blockade) or chemotherapy. TLR: toll-like receptor, HMGB1: high mobility group protein B1, MHC: major histocompatibility complex, PD-1: programmed cell death-1
See this image and copyright information in PMC

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