收稿日期: 2025-03-10
网络出版日期: 2025-06-19
基金资助
甘肃省级科技计划(创新基地和人才计划)自然科学基金(21JR7RH895);武威市市级科技计划项目(WW24B01SF008)
The application of autologous NK cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients with advanced renal cell carcinoma
Received date: 2025-03-10
Online published: 2025-06-19
目的 研究自体自然杀伤(NK)细胞在晚期肾细胞癌治疗中的应用及患者免疫功能、肿瘤标志物变化情况。 方法 选取2023年3月至2024年4月武威肿瘤医院收治的61例晚期肾细胞癌患者,根据患者治疗意愿结合倾向性评分匹配分为靶向组(31例,给予支持治疗联合苹果酸舒尼替尼胶囊治疗)和细胞组(30例,在靶向组基础上联合自体NK细胞),以6周为1个治疗周期,均治疗4个周期。统计两组治疗4个周期后临床疗效及治疗期间不良反应发生情况,比较两组治疗前和治疗4个周期后血清细胞因子、肿瘤标志物水平、淋巴细胞功能及免疫功能。 结果 治疗4个周期后,细胞组客观缓解率和疾病控制率均高于靶向组(P < 0.05)。两组治疗4个周期后血清低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、血小板衍化生长因子(PDGF)、癌胚抗原、糖类抗原125、糖类抗原199、甲胎蛋白水平与治疗前比较均降低,细胞组低于靶向组(P < 0.012 5)。两组治疗4个周期后血清细胞白介素-2、白细胞介素-6、肿瘤坏死因子-β、γ干扰素、外周血CD3+、CD4+、NK细胞水平及CD4+/CD8+与治疗前比较,均升高,细胞组血清白细胞介素-2、肿瘤坏死因子-β、γ干扰素、外周血CD3+、NK细胞水平高于靶向组(P < 0.012 5);外周血CD8+水平与治疗前比较,降低(P < 0.012 5),但组间比较差异无统计学意义(P > 0.012 5)。治疗期间,细胞组腹泻、恶心呕吐、脱发、肝功能损害、血小板水平降低、中性粒细胞水平降低发生率与靶向组比较,差异无统计学意义(P > 0.05)。 结论 自体NK细胞治疗晚期肾细胞癌可改善患者血清细胞因子水平,降低肿瘤标志物水平,调节机体淋巴细胞功能和免疫功能,具有较好的治疗效果,同时不会增加不良反应的发生,安全性良好。
唐俊天 , 聂蓬 , 肖永平 , 黄颖元 , 杨云 , 闫建宏 . 自体NK细胞在晚期肾细胞癌治疗中的应用及对患者免疫功能、肿瘤标志物的影响[J]. 实用医学杂志, 2025 , 41(11) : 1674 -1680 . DOI: 10.3969/j.issn.1006-5725.2025.11.010
Objective To study the application of autologous natural killer (NK) cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients. Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group (31 cases, given supportive treatment combined with sunitinib malate capsules) and cell group (30 cases, autologous NK cells combined with targeting group) according to the patient 's willingness to treat combined with propensity score matching. 6 weeks was a treatment cycle, and all patients were treated for 4 cycles. The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed. The levels of serum cytokines, tumor markers, lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment. Results After 4 cycles of treatment, the objective remission rate and disease control rate in the cell group were higher than those in the targeting group (P < 0.05). After 4 cycles of treatment, the levels of serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment, and those in the cell group were lower than those in the targeting group (P < 0.012 5). After 4 cycles of treatment, the levels of serum interleukin-2, interleukin-6, tumor necrosis factor-β, interferon-γ, peripheral blood CD3+, CD4+, NK cells and CD4+/CD8+in the two groups were higher than those before treatment. The levels of serum interleukin-2, tumor necrosis factor-β, interferon-γ, peripheral blood CD3+ and NK cells in the cell group were higher than those in the targeting group (P < 0.012 5). The level of CD8+ in peripheral blood was lower than that before treatment (P < 0.012 5), but there was no significant difference between the two groups (P > 0.012 5). During the treatment, there was no significant difference in the incidence of diarrhea, nausea and vomiting, alopecia, liver function damage, decreased platelet level and decreased neutrophil level between the cell group and the targeting group (P > 0.05). Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines, reduce the level of tumor markers, regulate the function of lymphocytes and immune function, and had a good therapeutic effect. At the same time, it would not increase the incidence of adverse reactions, and the safety was good.
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