抗原提呈细胞亚群预测肝癌患者的免疫治疗疗效研究

高舒玥; 程家敏; 赵飞宇; 千年松

doi:10.12435/j.issn.2095-5227.2024.032

抗原提呈细胞亚群预测肝癌患者的免疫治疗疗效研究

Predicting immunotherapy efficacy in patients with hepatocellular carcinoma by monitoring antigen presenting cell subsets

摘要

摘要:
背景原发性肝细胞癌(hepatocellular carcinoma，HCC)患者中免疫治疗应用广泛，但需寻找有效的疗效预测标志物，以此提供个体化和精准化的治疗。
目的探讨抗原提呈细胞(antigen presenting cell，APC)亚群与HCC患者免疫治疗的疗效关系。
方法前瞻性纳入2022年5月到2023年9月在解放军总医院第五医学中心初次接受免疫治疗的中晚期HCC患者，通过流式细胞仪检测免疫治疗前的B细胞/淋巴细胞(B/LYM)、巨噬细胞/所有核细胞(MA/TNC) 树突细胞/所有核细胞(DC/TNC)的数值。根据均值将患者分为高水平组和低水平组，并比较两组间无进展生存期(progression free survival，PFS)，并通过Cox分析影响PFS的因素。最后利用ROC曲线预测疾病控制的效能。
结果共纳入84人，中位年龄为57岁；男性患者58例，女性患者26例，APC亚群基线数据：B/LYM均值为16.54 ± 6.27%，MA/TNC均值为9.14 ± 2.87%，DC/TNC均值为0.051 ± 0.021%。Kaplan-Meier生存分析和Cox回归分析显示B/LYM高值组患者的mPFS显著高于低值组(5.90 vs 5.50个月，P=0.019；HR：0.588，95% CI：0.358 ~ 0.966)，MA/TNC低值组患者的mPFS显著高于高值组(7.20 vs 5.40个月，P=0.034；HR：0.617，95% CI：0.374 ~ 1.019)，DC/TNC患者High组的mPFS显著高于Low值组(6.30 vs 5.50个月，P=0.026；HR：0.615，95% CI：0.378 ~ 0.955)。且高水平的MA/TNC是疾病进展的独立危险因素，高水平的DC/TNC、B/LYM是疾病进展的保护因素。基线B/LYM、MA/TNC、DC/TNC对HCC患者接受2周期治疗后的疾病控制而言，具有较好的预测效能，且联合应用时效能进一步提高，AUC分别为0.685、0.723、0.745、0.865。
结论高水平的DC/TNC、B/LYM和低水平的MA/TNC的HCC患者，可能更容易从免疫治疗中获益。

Abstract:
Background Immunotherapy is widely used in patients with hepatocellular carcinoma (HCC), but it is necessary to search for effective prognostic markers to provide personalized and precise treatment.
Objective To investigate the relationship between antigen presenting cell (APC) subsets and immunotherapy efficacy in HCC patients.
Methods Prospectively, advanced HCC patients receiving initial immunotherapy at the Fifth Medical Center of Chinese PLA General Hospital were enrolled from May 2022 to September 2023, and blood was collected before immunotherapy, and the antigen presenting cell (APC) were detected by flow cytometry technology. The patients were divided into high and low groups according to the mean value, and the progression free survival (PFS) between the two groups was compared, and the factors affecting PFS were analyzed by Cox analysis. Finally, the ROC curve was used to predict the effectiveness of disease control.
Results A total of 84 participants were enrolled, with a median age of 57 years. There were 58 male patients and 26 female patients. The baseline data of APC showed that the mean B/LYM was 16.54 ± 6.27%, the mean MA/TNC was 9.14 ± 2.87%, and the mean DC/TNC was 0.051 ± 0.021%. Kaplan-Meier survival analysis and Cox regression analysis showed that mPFS in the high B/LYM group was significantly higher than that in the low group (5.90 vs 5.50 months, P=0.019; HR: 0.588, 95% CI: 0.358-0.966), mPFS in the low MA/TNC group was significantly higher than that in the high group (7.20 vs 5.40 months, P=0.034; HR: 0.617, 95% CI: 0.374-1.019), mPFS in DC/TNC patients of high group was significantly higher than that in the low group (6.30 vs 5.50 months, P=0.026; HR: 0.615, 95% CI: 0.378-0.955). High levels of MA/TNC were independent risk factors for disease progression, and high levels of DC/TNC and B/LYM were protective factors for disease progression. Baseline B/LYM, MA/TNC, and DC/TNC showed good predictive efficacy for disease control in HCC patients after 2 cycles of treatment, and the efficacy was further improved when they were in combination, with AUC of 0.685, 0.723, 0.745, and 0.865 respectively.
Conclusion HCC patients with high levels of DC/TNC, B/LYM, and low levels of MA/TNC may be more likely to benefit from immunotherapy.

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