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

Eun Kyung Jung; Tan-Huy Chu; Manh-Cuong Vo; Huy Phuoc Quang Nguyen; Dong Hoon Lee; Joon Kyoo Lee; Sang Chul Lim; Sung-Hoon Jung; Tae-Mi Yoon; Mee Sun Yoon; Duck Cho; Je-Jung Lee; Hyong-Ho Cho

doi:10.1016/j.jcyt.2022.05.004

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

Cytotherapy. 2022 Sep;24(9):905-915. doi: 10.1016/j.jcyt.2022.05.004. Epub 2022 Jun 29.

Authors

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea.
² Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea; Department of Biomedical Science, Chonnam National University Graduate School, Gwangju, South Korea.
³ Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
⁴ Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, South Korea; Department of Biomedical Science, Chonnam National University Graduate School, Gwangju, South Korea.
⁵ Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, South Korea.
⁶ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁷ Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea; Department of Biomedical Science, Chonnam National University Graduate School, Gwangju, South Korea. Electronic address: [email protected].
⁸ Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea.

PMID: 35778350
DOI: 10.1016/j.jcyt.2022.05.004

Abstract

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 augment 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 interleukin (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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Chemoradiotherapy
Cytotoxicity, Immunologic
Head and Neck Neoplasms* / therapy
Humans
Immunotherapy / methods
Killer Cells, Natural*
Squamous Cell Carcinoma of Head and Neck / metabolism
Squamous Cell Carcinoma of Head and Neck / therapy