4.5 Article

Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer

Journal

CYTOTHERAPY
Volume 24, Issue 9, Pages 905-915

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2022.05.004

Keywords

chemoradiation; head and neck squamous cell carcinoma; lymphocyte function-associated antigen 1 (LFA-1); natural killer cells; NKG2D

Funding

  1. National Research Foundation of Korea (NRF) - Korea government [NRF-2020R1A5A2031185, NRF-2020R1A2C2010098]
  2. National Research Foundation (NRF) - Korean government (MSIT) [NRF-2020M3A9G3080330]
  3. Chonnam National University Hwasun Hospital Institute for Biomedical Science [NRF-2020R1A5A2031185]
  4. [HCRI20042]

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This study assessed the potential of irradiation and cisplatin as a chemoradiotherapy regimen to enhance the effects of NK cell immunotherapy in HNSCC. The results showed that chemoradiotherapy induced NK cell activation and enhanced the cytotoxicity of NK cells against HNSCC. The combination of NK cells and chemoradiotherapy has a potent anti-tumor effect in HNSCC.
Background: The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to aug-ment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC).Methods: NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound inter-leukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors.Results: The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function-associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1,-2 and-3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC.Conclusions: Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.(c) 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

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