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Immunotherapy for head and neck cancer: latest developments and clinical potential.

ABSTRACT: Head and neck squamous cell cancer (HNSCC) is a malignancy with a rapidly changing demographic profile, given the recent epidemic of human papilloma virus related cancers. Most patients present with locally advanced disease and receive combination therapeutic approaches with curative potential, albeit with significant toxicity. Up to a third of patients, however, will eventually develop recurrent or metastatic disease. The prognosis of such patients is dismal, as palliative treatment options remain limited. Immune-directed therapies offer a novel therapeutic strategy beyond cytotoxic chemotherapy and are currently being evaluated in a wide variety of malignancies. HNSCC is a particularly favorable disease for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of HNSCC. This review focuses on the latest developments in immunotherapy in HNSCC, with a particular focus on checkpoint inhibitors, adoptive cellular therapies, and vaccines.

SUBMITTER: Bauml JM

PROVIDER: S-EPMC4872249 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Immunotherapy for head and neck cancer: latest developments and clinical potential.

Bauml Joshua M JM Cohen Roger B RB Aggarwal Charu C

Therapeutic advances in medical oncology 20160216 3

Head and neck squamous cell cancer (HNSCC) is a malignancy with a rapidly changing demographic profile, given the recent epidemic of human papilloma virus related cancers. Most patients present with locally advanced disease and receive combination therapeutic approaches with curative potential, albeit with significant toxicity. Up to a third of patients, however, will eventually develop recurrent or metastatic disease. The prognosis of such patients is dismal, as palliative treatment options rem ...[more]

PMID: 27239235

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Project description:The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients with HNSCC respond to immune checkpoint inhibitors, underscoring the critical need to alleviate cancer resistance to immunotherapy. Major advances have been made to elucidate the intrinsic and adaptive resistance mechanisms to immunotherapy. Central genomic events in HNSCC have been found to possess previously unknown roles in suppressing immune sensing. Such inhibitory function affects both the innate and adaptive arms of tumor-specific immunity. While checkpoint blockade effectively reinvigorates adaptive T-cell responses, additional targeting of the oncogenic inhibitors of innate immune sensing likely informs a novel and potent strategy for immune priming. This review discusses the recent advances on the identification of key HNSCC oncogenes that impair antitumor immunity and emerging immune-priming approaches that sensitize poorly immunogenic HNSCCs to checkpoint blockade. These approaches include but are not limited to cancer vaccine systems utilizing novel type I interferon agonists as immune adjuvants, radiation, DNA damage-inducing agents, and metabolic reprogramming. The goal of these multipronged approaches is to expand tumor-specific effector T-cells, break checkpoint receptor-mediated tolerance, and metabolically support sustained T-cell activation. The translation of therapeutics that reverses oncogenic inhibition of immune sensing requires thorough characterization of the HNSCC regulators of innate immune sensors, development of additional immunocompetent HNSCC mouse models, as well as engineering of more robust immune adjuvant delivery systems. Built on the success of checkpoint blockade, validation of novel immune-priming approaches holds key promises to expand the pool of responders to immunotherapy.

Dataset Information

Immunotherapy for head and neck cancer: latest developments and clinical potential.

Publications

Immunotherapy for head and neck cancer: latest developments and clinical potential.

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