Immunobiology Of The Head And Neck

Author : Kourtney Lynn Kostecki
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (145 download)

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Download or read book Modulation of the Head and Neck Cancer Tumor Immune Microenvironment by the Tam Family of Receptor Tyrosine Kinases written by Kourtney Lynn Kostecki and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Head and neck cancer (HNC) is a highly aggressive disease that arises from the mucosal surfaces of the aerodigestive tract and impacts millions of people worldwide, with over 900,000 new cases diagnosed globally each year. Unfortunately, the prognosis for late-stage disease remains poor despite the development of new treatments like immunotherapies.In order to escape the immune system and promote tumor growth, HNC cells alter their own proteome to manipulate the tumor immune microenvironment (TIME). Typically, the TIME in HNC is considered immunosuppressive and is infiltrated by anti-inflammatory cell types such as regulatory T cells, myeloid-derived suppressor cells, and M2-polarized macrophages. The TAM family of receptor tyrosine kinases (RTKs) is known to be heavily involved in regulation of both macrophage polarization status and the innate immune system in the non-cancer setting. The TAM family of RTKs (Tyro3, Axl, MerTK), beyond their role in innate immunity, have been shown to be involved in cancer progression. Previous studies in our laboratory have demonstrated that Axl is a critical driver of proliferation, survival, metastasis, and therapeutic resistance in HNC, and that MerTK is, at least in part, functionally redundant to Axl. In the non-cancer setting, the TAMs regulate portions of the innate immune response, and, in the context of HNC, the TAMs drive cancer progression. Presented within is the discovery of TAM regulation of the immune compartment in the HNC TIME. Genetic targeting of Axl resulted in a more pro-inflammatory TIME via increased recruitment and activation of natural killer cells. Simultaneous pharmacologic targeting of Axl and MerTK increased the levels of pro-inflammatory cells in the TIME, slowed tumor growth, and increased the efficacy of immune checkpoint inhibitors (ICIs). Thus, targeting the TAMs in HNC, alone or in combination with existing ICIs, may improve ICI response rates and result in more positive clinical outcomes for HNC patients.