卡瑞利珠单抗联合化疗药物热灌注对原发性肝癌PD-1/PD-L1信号通路的影响

doi:10.3969/j.issn.1006-6233.2023.11.033

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摘要 目的: 探究基于PD-1/PD-L1信号通路探究卡瑞丽珠单抗联合化疗药物热灌注治疗原发性肝癌的作用机制。方法: 选取我院于2019年2月至2021年3月收治的中晚期PHC患者80例,随机分为化疗药物热灌注组和卡瑞利珠单抗联合组,每组40例。化疗药物热灌注组给予化疗药物热灌注治疗,卡瑞利珠单抗联合组在化疗药物热灌注治疗后,给予卡瑞利珠单抗联合治疗。比较两组患者近期临床疗效;流式细胞仪检测血清中肿瘤标志物(CEA、AFP、AFP-L3)及T淋巴细胞亚群变化;比较肝功能指标(ALT、AST、TBIL、ALP);检测外周血中PD-1和PD-L1表达;比较不良反应发生率;对患者进行随访,采用Kaplan-Meier绘制生存曲线比较生存率。结果: 卡瑞利珠单抗联合组患者近期临床疗效、外周血中CD4⁺、CD8⁺、CD4⁺/CD8⁺比值高于化疗药物热灌注组,血清中AFP、AFP-L3、CEA水平、ALT、AST、TBIL、ALP水平及外周血中PD-1和PD-L1表达均低于化疗药物热灌注组(P<0.05)。卡瑞利珠单抗联合组疼痛发生率较化疗药物热灌注组降低,生存率较化疗药物热灌注组升高(P<0.05)。结论: 卡瑞利珠单抗联合化疗药物热灌注可通过抑制PD-1/PD-L1信号通路激活T淋巴细胞亚群,从而提高机体抗肿瘤免疫功能,延长患者生存期并减少疼痛,值得临床推广。

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关键词 ：原发性肝癌, PD-1/PD-L1信号通路, 卡瑞利珠单抗

Abstract：Objective: To explore the mechanism of action of camrelizumab combined with chemotherapy and hyperthermic perfusion in the treatment of primary liver cancer based on the PD-1/PD-L1 signaling pathway. Methods: Eighty patients with advanced primary hepatocellular carcinoma (PHC) treated in the hospital from February 2019 to March 2021 were randomly divided into two groups:a chemotherapy and hyperthermic perfusion group and an apatinib plus chemotherapy and hyperthermic perfusion group,each consisting of 40 patients.The chemotherapy and hyperthermic perfusion group received chemotherapy and hyperthermic perfusion treatment,while the apatinib plus chemotherapy and hyperthermic perfusion group received apatinib plus chemotherapy and hyperthermic perfusion treatment after the initial treatment.Short-term clinical efficacy was compared between the two groups.Flow cytometry was used to assess changes in tumor markers (CEA,AFP,AFP-L3) and T lymphocyte subsets.Liver function indexes (ALT,AST,TBIL,ALP) were compared.PD-1 and PD-L1 expression in peripheral blood were assessed,and the incidence of adverse reactions was compared.Kaplan-Meier survival analysis was conducted during patient follow-up to compare survival rates. Results: In the apatinib plus chemotherapy and hyperthermic perfusion group,short-term clinical efficacy and peripheral blood CD4⁺,CD8⁺,and CD4⁺/CD8⁺ ratio were higher compared to the chemotherapy and hyperthermic perfusion group.Levels of AFP,AFP-L3,CEA,ALT,AST,TBIL,ALP,PD-1,and PD-L1 expression in peripheral blood were lower in the apatinib combination group (P<0.05).The apatinib combination group had a lower incidence of pain and a higher survival rate compared to the chemotherapy and hyperthermic perfusion group (P<0.05). Conclusion: The combination of camrelizumab and chemotherapy and hyperthermic perfusion can activate T lymphocyte subsets by inhibiting the PD-1/PD-L1 signaling pathway,thereby improving the body's anti-tumor immune function,prolonging the survival period of patients,and reducing pain.This approach is worth promoting in clinical practice.

Key words： Primary liver cancer PD-1/PD-L1 signaling pathway Carrilizumab

基金资助:2022年度蚌埠医学院省重点科研平台开放课题,(编号:2022SYKFD03)

通讯作者: 李阳

引用本文:

姜磊, 刘成, 孙万亮, 周凯, 王超, 李阳. 卡瑞利珠单抗联合化疗药物热灌注对原发性肝癌PD-1/PD-L1信号通路的影响[J]. 河北医学, 2023, 29(11): 1927-1933.
JIANG Lei, LIU Cheng, SUN Wanliang, et al. Impact of Camrelizumab Combined with Chemotherapy and Hyperthermic Perfusion on the PD-1/PD-L1 Signaling Pathway in Primary Liver Cancer. HeBei Med, 2023, 29(11): 1927-1933.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.11.033 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I11/1927

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