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Exploring the rationale for combining ionizing radiation and immune checkpoint blockade in head and neck cancer.

ABSTRACT: BACKGROUND:The ability of radiation to enhance antitumor immunity under specific experimental conditions is well established. Here, we explore preclinical data and the rationale for combining different radiation doses and fractions with immune checkpoint blockade immunotherapy. METHODS:We conducted a review of the literature. RESULTS:The ability of high-dose or hypofractionated radiation to enhance antitumor immunity resulting in additive or synergistic tumor control when combined with checkpoint blockade is well studied. Whether low-dose daily fractionated radiation does the same is less well studied and available data suggests it may be immunosuppressive. CONCLUSION:Although daily fractionated radiation is well established as the standard of care for the treatment of patients with head and neck cancer, how this radiation schema alters antitumor immunity needs further study. If the radiation doses and fractions alter antitumor immunity differently can have profound implications in the rational design of clinical trials investigating whether radiation can enhance response rates to immune checkpoint blockade.

SUBMITTER: Morisada M

PROVIDER: S-EPMC5980679 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Exploring the rationale for combining ionizing radiation and immune checkpoint blockade in head and neck cancer.

Morisada Megan M Chamberlin Michael M Allen Clint C

Head & neck 20180220 6

<h4>Background</h4>The ability of radiation to enhance antitumor immunity under specific experimental conditions is well established. Here, we explore preclinical data and the rationale for combining different radiation doses and fractions with immune checkpoint blockade immunotherapy.<h4>Methods</h4>We conducted a review of the literature.<h4>Results</h4>The ability of high-dose or hypofractionated radiation to enhance antitumor immunity resulting in additive or synergistic tumor control when c ...[more]

PMID: 29461655

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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

Exploring the rationale for combining ionizing radiation and immune checkpoint blockade in head and neck cancer.

Publications

Exploring the rationale for combining ionizing radiation and immune checkpoint blockade in head and neck cancer.

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