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DOI: 10.1055/s-0040-1710968
Effects of the PD-1 PD-L1 signaling pathway on the functionality of NK cells in the tumor microenvironment of patients with head and neck cancer
Introduction Cetuximab causes NK cell mediated antitumor responses through Antibody Dependant Cellular Cytotoxicity. However, only a minority of patients show therapeutic responses. Therefore, we investigated the importance of the PD-1/ PD-L1 signaling pathway for the NK cell Activity of Patients with Head and Neck Cancer.
Methods. Tumor and blood specimen of 74 patients with Head and Neck Cancer were analyzed. The cytotoxicity of isolated NK cells was evaluated by 51Cr release Assay. Additionally, we performed immunohistochemistry and RNA analysis.
Results Activated NK cells of the tumor microenvironment express PD-1. The ligation of PD-L1 results in an inactivation of these cells. A blockade of this signaling pathway results in an increased Antibody Dependant Cellular Cytotoxicity of cetuximab.
Discussion The NK cell mediated Antibody Dependant Cellular Cytotoxicity is inhibited by the PD-1/ PD-L1 signaling pathway in the tumor microenvironment of patients with Head and Neck Cancer. A blockade of this pathway results in an NK cell activation and represents a new approach for combinational therapies.
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Artikel online veröffentlicht:
10. Juni 2020
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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