Ek-Eudomsuk Pornpimon, Chalermrujinanant Chonvara, Soontrapa Kitipong
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Asian Pac J Allergy Immunol. 2022 Mar 12. doi: 10.12932/AP-280921-1245.
Cytokine-induced killer (CIK) cells are an ex vivo expanded heterogeneous population of natural killer (NK)-like T cells that can exert potent MHC-unrestricted antitumor activity. A number of pre-clinical and clinical studies have demonstrated that CIK cells can serve as a safe and potent immunotherapy of malignant tumors. N-acetylcysteine (NAC) has been demonstrated to enhance the T-cell functions by increasing their proliferation and cytokine production.
To investigate whether the incorporation of NAC to CIK cell culture could enhance the antitumor activity of CIK cells.
The phenotypes of human CIK cells, including CD3+CD56+, IFN-γ, granzyme B, and perforin, were determined by flow cytometry. The cytotoxic activity against the human erythroleukemic cell line (K562) and cholangiocarcinoma cell line (CL6) prelabeled with CFSE was investigated by flow cytometry. The mRNA expression levels of IFNG, PRF1, and GZMB were measured by real-time PCR.
By adding NAC into CIK cell culture, the percentage of CD3+CD56+ cells along with the expression of Th1 cytokines and cytolytic granules increased significantly, resulting in an improvement of cytotoxicity against the cancer cell lines CL6 and K562.
The incorporation of NAC into CIK culture can markedly improve the cytotoxicity against cancer cells due to the significant increase in the major effector population of CIK cells expressing Th1 cytokines and cytolytic granules.
细胞因子诱导的杀伤（CIK）细胞是体外扩增的异质性自然杀伤（NK）样T细胞群体，可发挥强大的主要组织相容性复合体（MHC）非限制性抗肿瘤活性。多项临床前和临床研究表明，CIK细胞可作为一种安全有效的恶性肿瘤免疫疗法。已证明N-乙酰半胱氨酸（NAC）可通过增加T细胞增殖和细胞因子产生来增强其功能。
研究在CIK细胞培养中加入NAC是否能增强CIK细胞的抗肿瘤活性。
采用流式细胞术检测人CIK细胞的表型，包括CD3+CD56+、干扰素-γ（IFN-γ）、颗粒酶B和穿孔素。采用流式细胞术研究对用羧基荧光素二乙酸琥珀酰亚胺酯（CFSE）预标记的人红白血病细胞系（K562）和胆管癌细胞系（CL6）的细胞毒性活性。采用实时聚合酶链反应（PCR）检测IFNG、PRF1和GZMB的信使核糖核酸（mRNA）表达水平。
在CIK细胞培养中加入NAC后，CD3+CD56+细胞百分比以及Th1细胞因子和溶细胞颗粒的表达显著增加，从而提高了对癌细胞系CL6和K562的细胞毒性。
在CIK培养中加入NAC可显著提高对癌细胞的细胞毒性，这是由于表达Th1细胞因子和溶细胞颗粒 的CIK细胞主要效应群体显著增加所致。
