P37 BTK inhibitor Ibrutinib regulates the TLR3 induced IL-1ß expression in HNSCC. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Lanka, A.; Pries, R.; Wollenberg, B.
• Is Part Of: Oral oncology. Volume 51:Issue 5(2015:May)
• Page Start: e54
• Publication Date: 2015-05
• Subjects: Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2015.02.085
• Languages: English
• ISSNs: 1368-8375

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title id="st005">Introduction</title> <p id="sp005">Ibrutinib is the first drug designed to inhibit Burton's tyrosine kinase (BTK) activity. It is a new targeted therapy for chronic lymphocytic leukemia (CLL). BTK plays a critical role in humoral immune responses and is essential mediator for the growth and survival of B-Cells. Several unknown underlying immunosuppressive mechanisms are involved in the development of Head and Neck Squamous Cell Carcinomas (HNSCCs) worldwide.</p> </sec> <sec> <title id="st010">Material and methods</title> <p id="sp010">To investigate how the BTK inhibitor Ibrutinib influences the progression and microenvironment biosynthesis in HNSCC, different established HNSCC cell lines were treated with Ibrutinib and triggered with the TLR3 ligand Polyinosinic:polycytidylic acid (PolyI:C) through both extracellular and intracellular ways.</p> </sec> <sec> <title id="st015">Results</title> <p id="sp015">This resulted in reduced expression levels of immunomodulatory cytokines IL-1<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgjcwgwr0b" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" overflow="scroll" id="d13e58" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> and IL-8. Furthermore, our data demonstrate an efficient suppression of the extracellular-signal regulated kinase1/2 (ERK1/2) MAPK as well as significantly reduced cell viability.</p> </sec> <sec> <title id="st020">Conclusion</title> <p id="sp020">Therefore, Ibrutinib could be a new and promising approach to unfold the underlying immunosuppressive mechanisms involved in HNSCC.</p> </sec> </abstract>