Yang Wenzhuo, Chen Haodong, Zhang Zhilan, Xia Zhiyong, Jin Yuanyuan, Yang Zhaoyong
The Department of Oncology, Beijing Hospital, Beijing, 100034, China.
NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, 100050, China.
Oncol Res. 2025 May 29;33(6):1485-1494. doi: 10.32604/or.2025.059426. eCollection 2025.
Human natural killer (NK) cells have attracted widespread attention as a potential adoptive cell therapy (ACT). However, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. There is an urgent need to explore a suitable new treatment plan to overcome weaknesses and support the superior therapeutic activity of NK cells.
In this study, the mechanisms underlying the susceptibility of gastric cancer (GC) cell lines AGS, HGC-27, and NCI-N87 to NK cell-mediated cytotoxicity were explored.
Lactic dehydrogenase (LDH) release assays showed that all three GC cell lines were susceptible to the umbilical cord blood NK (UCB-NK) cells, and HGC-27 cells with high CD56 expression were the most sensitive to UCB-NK, followed by NCI-N87 and AGS. When the expression of CD56 in HGC-27 cells decreased, the lytic activity of NK cells in HGC-27 cells was abating. In addition, combining oxaliplatin with NK cells produced additive anti-tumor effects , which may have resulted from oxaliplatin-induced NK group 2 member D (NKG2DL) upregulation in GC cells. These results of cytotoxicity activity showed that inhibition of CD56 expression might suppress the sensitivity of GC cells to NK cell-mediated cytotoxicity, and upregulation of the expression of NKG2DL on the surface of GC cells by oxaliplatin could enhance the killing sensitivity of NK cells.
Collectively, our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC.
人类自然杀伤（NK）细胞作为一种潜在的过继性细胞疗法（ACT）已引起广泛关注。然而，NK细胞输注对实体瘤患者的治疗效果有限。迫切需要探索一种合适的新治疗方案，以克服弱点并支持NK细胞的卓越治疗活性。
在本研究中，探讨了胃癌（GC）细胞系AGS、HGC - 27和NCI - N87对NK细胞介导的细胞毒性敏感性的潜在机制。
乳酸脱氢酶（LDH）释放试验表明，所有三种GC细胞系均对脐带血NK（UCB - NK）细胞敏感，且CD56表达高的HGC - 27细胞对UCB - NK最敏感，其次是NCI - N87和AGS。当HGC - 27细胞中CD56表达降低时，HGC - 27细胞中NK细胞的裂解活性减弱。此外，奥沙利铂与NK细胞联合产生了相加的抗肿瘤作用，这可能是由于奥沙利铂诱导GC细胞中NK组2成员D（NKG2DL）上调所致。这些细胞毒性活性结果表明，抑制CD56表达可能会抑制GC细胞对NK细胞介导的细胞毒性的敏感性，而奥沙利铂上调GC细胞表面NKG2DL的表达可增强NK细胞的杀伤敏感性。
总体而言，我们的研究为NK细胞免疫疗法治疗人类GC提供了更深入的理论基础和更好的治疗策略。
