Wang Jun-Feng, Zhang Lu-Zhou, Liu Tao, Meng Qing-Hong, Mu Jia-Wei, Wang Yu-Liang
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.
Department of Gastrointestinal Surgery, Zhucheng People's Hospital, Zhucheng 262200, Shandong Province, China.
World J Gastrointest Oncol. 2025 May 15;17(5):104591. doi: 10.4251/wjgo.v17.i5.104591.
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.
To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19 (CRC patients).
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.
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.
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.
严重急性呼吸综合征冠状病毒2引发的2019冠状病毒病（COVID-19）给全球公共卫生带来了巨大挑战，同时也增加了患结直肠癌（CRC）的易感性。自然杀伤（NK）细胞是宿主固有免疫系统的第一道防线，具有自然杀伤功能，并介导对肿瘤和病毒的细胞毒性作用。因此，更好地了解NK细胞的细胞毒性可能有助于开发与COVID-19相关的CRC治疗策略。
研究CRC合并重症COVID-19患者（CRC患者）外周血NK细胞的细胞毒性杀伤功能。
采用流式细胞术分析CRC患者及年龄匹配的CRC患者循环NK细胞和NKT细胞的百分比。使用实时细胞分析仪评估外周血单个核细胞中的NK细胞细胞毒性活性（NKCA）和相应的NK细胞毒性因子（NKCF）活性。
CRC患者外周血NK细胞和NKT细胞的数量及百分比低于CRC患者。此外，与CRC患者相比，CRC患者裂解的K562细胞中NKCA和NKCF活性水平较低。在CRC患者中，NKCA与NK细胞数量、NKCA与NK细胞百分比、NKCF活性以及NK细胞百分比之间存在正相关。此外，在CRC患者中，NKCA与COVID-19的严重程度之间存在负相关。NKCA的受试者工作特征曲线下面积大于其他指标。
CRC与外周血NK细胞水平降低和自然细胞毒性受损有关，这导致了重症COVID-19的免疫发病机制，而非免疫控制。
