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Immune-relevant aspects of murine models of head and neck cancer.

ABSTRACT: Head and neck cancers (HNCs) cause significant mortality and morbidity. There have been few advances in therapeutic management of HNC in the past 4 to 5 decades, which support the need for studies focusing on HNC biology. In recent years, increased recognition of the relevance of the host response in cancer progression has led to novel therapeutic strategies and putative biomarkers of tumor aggressiveness. However, tumor-immune interactions are highly complex and vary with cancer type. Pre-clinical, in vivo models represent an important and necessary step in understanding biological processes involved in development, progression and treatment of HNC. Rodents (mice, rats, hamsters) are the most frequently used animal models in HNC research. The relevance and utility of information generated by studies in murine models is unquestionable, but it is also limited in application to tumor-immune interactions. In this review, we present information regarding the immune-specific characteristics of the murine models most commonly used in HNC research, including immunocompromised and immunocompetent animals. The particular characteristics of xenograft, chemically induced, syngeneic, transgenic, and humanized models are discussed in order to provide context and insight for researchers interested in the in vivo study of tumor-immune interactions in HNC.

SUBMITTER: Rossa C

PROVIDER: S-EPMC6533118 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Immune-relevant aspects of murine models of head and neck cancer.

Rossa Carlos C D'Silva Nisha J NJ

Oncogene 20190129 21

Head and neck cancers (HNCs) cause significant mortality and morbidity. There have been few advances in therapeutic management of HNC in the past 4 to 5 decades, which support the need for studies focusing on HNC biology. In recent years, increased recognition of the relevance of the host response in cancer progression has led to novel therapeutic strategies and putative biomarkers of tumor aggressiveness. However, tumor-immune interactions are highly complex and vary with cancer type. Pre-clini ...[more]

PMID: 30696955

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Project description:BackgroundThe mechanisms driving multiple sclerosis (MS), the most common cause of non-traumatic disability in young adults, remain unknown despite extensive research. Especially puzzling are the underlying molecular processes behind the two major disease patterns of MS: relapsing-remitting and progressive. The relapsing-remitting course is exemplified by acute inflammatory attacks, whereas progressive MS is characterized by neurodegeneration on a background of mild-moderate inflammation. The molecular and cellular features differentiating the two patterns are still unclear, and the role of inflammation during progressive disease is a subject of active debate.MethodsWe performed a comprehensive analysis of the intrathecal inflammation in two clinically distinct mouse models of MS: the PLP139-151-induced relapsing experimental autoimmune encephalomyelitis (R-EAE) and the chronic progressive, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Microarray technology was first used to examine global gene expression changes in the spinal cord. Inflammation in the spinal cord was further assessed by immunohistochemical image analysis and flow cytometry. Levels of serum and cerebrospinal fluid (CSF) immunoglobulin (Ig) isotypes and chemokines were quantitated using Luminex Multiplex technology, whereas a capture ELISA was used to measure serum and CSF albumin levels. Finally, an intrathecal Ig synthesis index was established with the ratio of CSF and serum test results corrected as a ratio of their albumin concentrations.ResultsMicroarray analysis identified an enrichment of B cell- and Ig-related genes upregulated in TMEV-IDD mice. We also demonstrated an increased level of intrathecal Ig synthesis as well as a marked infiltration of late differentiated B cells, including antibody secreting cells (ASC), in the spinal cord of TMEV-IDD, but not R-EAE mice. An intact blood-brain barrier in TMEV-IDD mice along with higher CSF levels of CXCL13, CXCL12, and CCL19 provides evidence for an intrathecal synthesis of chemokines mediating B cell localization to the central nervous system (CNS).ConclusionsOverall, these findings, showing increased concentrations of intrathecally produced Igs, substantial infiltration of ASC, and the presence of B cell supporting chemokines in the CNS of TMEV-IDD mice, but not R-EAE mice, suggest a potentially important role for Igs and ASC in the chronic progressive phase of demyelinating diseases.

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Immune-relevant aspects of murine models of head and neck cancer.

Publications

Immune-relevant aspects of murine models of head and neck cancer.

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