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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Natural killer cell dysfunction is associated with colorectal cancer with severe COVID-19
Jun-Feng Wang, Lu-Zhou Zhang, Tao Liu, Qing-Hong Meng, Jia-Wei Mu, Yu-Liang Wang
Jun-Feng Wang, Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Lu-Zhou Zhang, Department of Gastrointestinal Surgery, Zhucheng People’s Hospital, Zhucheng 262200, Shandong Province, China
Tao Liu, National Health Commission’s Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Tianjin 300071, China
Qing-Hong Meng, Department of Clinical Laboratory Medicine, Eco-city Hospital of Tianjin Fifth Central Hospital, Tianjin 300467, China
Jia-Wei Mu, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
Yu-Liang Wang, Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
Co-first authors: Jun-Feng Wang and Lu-Zhou Zhang.
Author contributions: Wang JF, Zhang LZ, Liu T, and Wang YL performed the experiments; Wang JF, Meng QH, Mu JW, and Wang YL acquired and analyzed the data; Wang JF, Zhang LZ, and Wang YL interpreted the data; Wang YL conceived and designed the project; Meng QH drafted the manuscript; Wang YL wrote the manuscript, conceptualized, and designed the project process; conducted the literature research, revised the manuscript, and handled its submission; All authors approved the final version of the article.
Institutional review board statement: The institutional review board of Tianjin Medical University Cancer Hospital approved the study protocol. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards, No. Ek2022110.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed supporting conclusions are included in the current manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Yu-Liang Wang, MD, PhD, Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, No. 22 Pingjiang Road, Hexi Distinct, Tianjin 300211, China.
wang_yu_l@163.com
Received: January 2, 2025
Revised: January 30, 2025
Accepted: February 27, 2025
Published online: May 15, 2025
Processing time: 134 Days and 0 Hours
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019 (COVID-19) has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer (CRC). Natural killer (NK) cells serve as the first line of defense in the host’s innate immune system, performing natural killing functions and mediating cytotoxicity against tumors and viruses. Therefore, a better understanding of NK cell cytotoxicity may facilitate the development of treatment strategies for CRC-associated with COVID-19.
AIM
To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19 (CRC+ patients).
METHODS
The percentages of circulating NK and NKT cells in CRC+ and age-matched patients with CRC were analyzed using flow cytometry. NK cell cytotoxic activity (NKCA) and corresponding NK cytotoxic factor (NKCF) activity in peripheral blood mononuclear cells were evaluated using a Real-Time Cell Analyzer.
RESULTS
The numbers and percentage of peripheral NK and NKT cells in patients with CRC+ were lower than those in patients with CRC. Additionally, compared to patients with CRC, those with CRC+ had lower levels of NKCA and NKCF activity in lysed K562 cells. Positive correlations were observed between NKCA and NK cell numbers, NKCA and NK cell percentages, NKCF activity, and NK cell percentages in patients with CRC+. Furthermore, a negative correlation was observed between NKCA and the severity of COVID-19 in patients with CRC. The area under the receiver operating characteristic curve for NKCA was greater than those for the other indices.
CONCLUSION
CRC+ is associated with lower levels of peripheral NK cells and impaired natural cytotoxicity, contributing to the immunopathogenesis of severe COVID-19 rather than immune control.
Core Tip: Severe acute respiratory syndrome coronavirus 2-induced coronavirus disease 2019 (COVID-19) has posed a great challenge to public health worldwide and has also increased susceptibility to colorectal cancer (CRC). As the first line of defense in the host’s innate immune system, natural killer (NK) cells play a key role in rapidly identifying and eliminating cancerous cells, viruses, and infected cells. In this investigation, patients with CRC and severe COVID-19 had lower levels of peripheral NK cells and impaired natural cytotoxicity, either through direct NK cell cytotoxic activity or NK cytotoxic factor release, thereby contributing to the immunopathogenesis of severe COVID-19 rather than immune control, at least to some extent.
