Natural Killer Cells as a Potential Biomarker for Predicting Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer



Immunotherapy with immune checkpoint inhibitors for non-small cell lung cancer (NSCLC) has emerged as an important treatment option. Although immunotherapy may significantly improve survival and quality of life, response rates are as low as 20% in NSCLC patients.


The identification of reliable biomarkers predicting response to immunotherapy is required urgently to determine patient selection guidelines.

Patients and Methods

Peripheral blood mononuclear cells (PBMCs) from nine NSCLC patients were collected pre- and post-treatment with immunotherapy. The immune cell composition of PBMCs was analyzed using CyTOF with an optimized 32-marker panel. The natural killer (NK) cell activity was assessed with the measurement of interferon (INF)-γ using an NK Vue™ kit.


We found that the percentages of NK cell populations in the immune cells of PBMCs were prominently elevated in the immunotherapy responder group when compared with non-responders. While no meaningful differences were observed in other populations of immune cells, consistent with these results, the overall activity of NK cells in responders was highly elevated compared with that of non-responders. From the analysis of NK subsets, although differences in the population of early NK cells were not observed, the functionally differentiated late NK cells were prominently high in responders.


The overall activity or number of NK cells may be a useful biomarker to predict immunotherapy response in patients with NSCLC.

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The authors thank the Optical Imaging Core at the ConveRgence mEDIcine Research Center (CREDIT), Asan Medical Center, for the use of their shared equipment, services, and expertise. They would also like to thank Enago ( for the English language review.

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Corresponding authors

Correspondence to Jin Kyung Rho or Chang-Min Choi.

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This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2019R1A2C2006054 to JKR) and a grant (2018-563 to JKR) from the Asan Institute for Life Sciences, Seoul, Korea.

Conflict of interest

Yong-Hee Cho, Myeong Geun Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Ki Jung Sung, Jae Cheol Lee, Sang-Yeob Kim, Jin Kyung Rho, and Chang-Min Choi declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Cho, YH., Choi, M.G., Kim, D.H. et al. Natural Killer Cells as a Potential Biomarker for Predicting Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer. Targ Oncol 15, 241–247 (2020).

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