Molecular Biology and Immunology of Head and Neck Cancer

Guo, Theresa; Califano, Joseph A.

doi:10.1016/j.soc.2015.03.002

Cited by 34 publications

(22 citation statements)

References 58 publications

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“…By contrast, HNSCC samples presented with IDO1 but only on a small fraction of tumorinfiltrating lymphocytes (Figure 2). Although not analyzed systematically, the only HPV positive case in this small cohort showed highest IDO1 abundance, nicely reflecting the tumors' immunogenicity (11,37). Using five individual GBM cell lines, IDO1 expression was inducible in all cases ( Figure 3A).…”

Section: Basal Ido1 and Related Genes In Gbm And Hnscc Cell Linesmentioning

confidence: 80%

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

et al. 2020

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Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2) are the key enzymes of tryptophan (TRP) metabolism in the kynurenine pathway (KP). Both enzymes function as indicators of immunosuppression and poor survival in cancer patients. Direct or indirect targeting of either of these substances seems thus reasonable to improve therapy options for patients. In this study, glioblastoma multiforme (GBM) as well as head and neck squamous cell carcinomas (HNSCC) were examined because of their different mechanisms of spontaneous and treatment-induced immune escape. Effects on gene expression and protein levels were examined. Accompanying assessment of TRP metabolites from treated GBM cell culture supernatants was conducted. Our results show a heterogeneous and inversely correlated expression profile of TRP-metabolizing genes among GBM and HNSCC cells, with low, but inducible IDO1 expression upon IFNγ treatment. TDO2 expression was higher in GBM cells, while genes encoding kynurenine aminotransferases were mainly confined to HNSCC cells. These data indicate that the KP is active in both entities, with however different enzymes involved in TRP catabolism. Upon treatment with Temozolomide, the standard of care for GBM patients, IDO1 was upregulated. Comparable, although less pronounced effects were seen in HNSCC upon Cetuximab and conventional drugs (i.e., 5-fluorouracil, Gemcitabine). Here, IDO1 and additional genes of the KP (KYAT1, KYAT2, and KMO) were induced. Vice versa, the novel yet experimental cyclin-dependent kinase inhibitor Dinaciclib suppressed KP in both entities. Our comprehensive data imply inhibition of the TRP catabolism by Dinaciclib, while conventional chemotherapeutics tend to activate this pathway. These data point to limitations of conventional therapy and highlight the potential of targeted therapies to interfere with the cells' metabolism more than anticipated.

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Section: Basal Ido1 and Related Genes In Gbm And Hnscc Cell Linesmentioning

confidence: 80%

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

et al. 2020

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“…12 Mounting evidence indicates that the transition from normal epithelium to PPOELs to invasive OSCC is the result of an accumulation of genetic and epigenetic alterations, the latter referring to a multitude of aberrations, including chromosomal rearrangements, mutations, methylation, and others, which affect the expression and function of oncogenes and tumor suppressor genes (reviewed elsewhere). 12,[14][15][16] In other words, the clinical appearance (e.g., OL) and microscopic changes (e.g., epithelial dysplasia) that indicate the presence of PPOELs are driven by specific molecular alterations that accumulate over time, eventually culminating in MT. Because, by definition, PPOELs and/or dysplasia are viewed as early events, it follows that elucidation of molecular alterations crucial to the progression to malignancy would predict premalignancy with greater specificity and sensitivity when coupled with clinical annotation and histopathology.…”

Section: The Potential Of Molecular Markersmentioning

confidence: 99%

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications

Nikitakis

Pentenero

Georgaki

et al. 2018

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Identification and management of potentially premalignant oral epithelial lesions (PPOELs) at highest risk of malignant transformation holds great promise for successful secondary prevention of oral squamous cell carcinoma, potentially reducing oral cancer morbidity and mortality. However, to date, neither clinical nor histopathologic validated risk predictors that can reliably predict which PPOELs will definitively progress to malignancy have been identified. In addition, the management of PPOELs remains a major challenge. Arguably, progress in the prevention and treatment of oral premalignancy and cancer will require improved understanding of the underlying molecular mechanisms, facilitating the discovery of diagnostic, prognostic, and predictive markers, as well as the identification of novel targeted therapeutics. This review provides a synopsis of the molecular biomarkers that have been studied in PPOELs and have been correlated with the presence and grade of dysplasia and/or their propensity to undergo malignant transformation to oral squamous cell carcinoma. The emphasis is on highlighting new emerging research fields, particularly epigenetic events, including methylation and micro-RNA regulation. Several promising biomarkers are highlighted. Current limitations and challenges are discussed. Recommendations for future focused research areas, to validate and promote clinically useful applications, are offered.

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“…Úvod V posledních několika letech se velmi významně změnil pohled na bio logickou podstatu celé řady onkologických onemocnění, nádory v oblasti hlavy a krku nevyjímaje, na podkladě přibývajících informací z oblasti molekulární genetiky, bio logie a imunologie [1]. Ně kte ré z těchto znalostí se již přímo uplatnily v klinické praxi, ně kte ré vykazují slibný potenciál do budoucnosti.…”

Section: S87unclassified

Immune System in Patients with Head and Neck Carcinoma

Partlová¹,

Bouček²,

Kloudová³

et al. 2015

Klin Onkol

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V posledních několika letech se významně změnil pohled na bio logickou podstatu nádorů v oblasti hlavy a krku. Klasickými prokázanými rizikovými faktory nádorů v oblasti hlavy a krku jsou kouření a konzumace alkoholu, resp. jejich kombinace. Pa cienti s nádory vzniklými na podkladě této etiologie se pohybují ve vyšších věkových skupinách, nejčastěji v pátém a šestém decéniu. Dále byla v posledních přibližně 15 letech prokázána souvislost s infekcí lidským papillomavirem (HPV), který je dnes považován za jeden z nejvýznamnějších rizikových faktorů, zejména pro karcinom orofaryngu. HPV pozitivní nádory orofaryngu jsou spojeny s významně lepší prognózou onemocnění. Výzkumná i klinická data ukazují, že HPV pozitivní a negativní nádory lze v mnoha ohledech považovat za dvě rozdílné entity a dosud není zcela objasněno, jaké faktory jsou klíčové pro lepší prognózu HPV pozitivní nádorů. Jedním z důležitých faktorů, který se podílí na rozdílné prognóze, může být charakter imunitní reakce. Tento článek shrnuje současné poznatky o různých aspektech protinádorové imunitní reakce u HPV pozitivních a negativních nádorů. Současné studie udávají, že téměř u všech HPV pozitivních pa cientů byly detekovány významné počty HPV specifi ckých T lymfocytů, v nádorové tkáni. I navzdory tomu však dochází k rozvoji nádoru, což může být způsobeno abnormalitami v antigenní prezentaci, dysfunkcemi T lymfocytů či přítomností různých populací imunosupresivních buněk. Imunologický profi l HPV pozitivních, resp. HPV negativních nádorů v oblasti hlavy a krku přesto jednoznačně koreluje s terapeutickými výsledky a HPV specifi cká imunitní odpověď má pravděpodobně zásadní význam při lepší odpovědi HPV pozitivních pa cientů na konvenční léčbu. Diskutujeme také vyvíjené postupy HPV specifi cké protinádorové imunoterapie, které jsou nyní ve fázi klinických zkoušek. Klíčová slova nádory hlavy a krku-lidský papillomavirus-imunitní systém-T lymfocyty-imunoterapie

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Molecular Biology and Immunology of Head and Neck Cancer

Cited by 34 publications

References 58 publications

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications

Immune System in Patients with Head and Neck Carcinoma

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