Division of Hematology-Oncology, Department of Internal Medicine, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
PLoS One. 2023 Jan 4;18(1):e0280023. doi: 10.1371/journal.pone.0280023. eCollection 2023.
Cytokine-induced killer (CIK) cells are heterogeneous lymphocytes from human peripheral blood mononucleated cells (PBMCs) co-cultured with several cytokines. The main purpose of this study is to evaluate the functional characteristics and anticancer ability of CIK cells from hepatocarcinoma (HCC) patients.
CIK cells were activated ex-vivo and expanded from PBMCs from HCC patients. The immunophenotype and the ex-vivo killing ability of CIK cells were evaluated. Human CIK cells were intravenously injected into NOD/SCID mice to evaluate the in vivo anticancer ability.
More than 70% of CIK cells were CD3+CD8+, and 15%-30% were CD3+CD56+. These cells expressed an increased number of activated natural killer (NK) receptors, such as DNAM1 and NKG2D, and expressed low-immune checkpoint molecules, including PD-1, CTLA-4, and LAG-3. Among the chemokine receptors expressed by CIKs, CXCR3 and CD62L were elevated in CD8+ T cells, representing the trafficking ability to inflamed tumor sites. CIK cells possess the ex-vivo anticancer activity to different cell lines. To demonstrate in vivo antitumor ability, human CIK cells could significantly suppress the tumor of J7 bearing NOD/SCID mice. Furthermore, human immune cells could be detected in the peripheral blood and on the tumors after CIK injection.
This study revealed that CIK cells from HCC patients possess cytotoxic properties, and express increased levels of effector NK receptors and chemokine molecules and lower levels of suppressive checkpoint receptors. CIK cells can suppress human HCC ex-vivo and in vivo. Future clinical trials of human CIK cell therapy for HCC are warranted.
细胞因子诱导的杀伤（CIK）细胞是从人外周血单个核细胞（PBMCs）与几种细胞因子共培养而来的异质淋巴细胞。本研究的主要目的是评估肝癌（HCC）患者来源的 CIK 细胞的功能特征和抗癌能力。
从 HCC 患者的 PBMCs 中外源激活并扩增 CIK 细胞。评估 CIK 细胞的免疫表型和体外杀伤能力。将人 CIK 细胞静脉注射到 NOD/SCID 小鼠体内，以评估其体内抗癌能力。
超过 70%的 CIK 细胞为 CD3+CD8+，15%-30%为 CD3+CD56+。这些细胞表达了更多的激活型自然杀伤（NK）受体，如 DNAM1 和 NKG2D，并且表达了低免疫检查点分子，包括 PD-1、CTLA-4 和 LAG-3。在 CIK 表达的趋化因子受体中，CD8+T 细胞中 CXCR3 和 CD62L 升高，代表向炎症肿瘤部位的迁移能力。CIK 细胞具有针对不同细胞系的体外抗癌活性。为了证明体内抗肿瘤能力，人 CIK 细胞可显著抑制 J7 荷瘤 NOD/SCID 小鼠的肿瘤生长。此外，在 CIK 注射后，人免疫细胞可在外周血和肿瘤中检测到。
本研究表明，来自 HCC 患者的 CIK 细胞具有细胞毒性，表达更高水平的效应 NK 受体和趋化因子分子，以及更低水平的抑制性检查点受体。CIK 细胞可抑制人 HCC 的体外和体内生长。需要进行前瞻性临床试验，以评估人 CIK 细胞治疗 HCC 的效果。
