Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2024 Jan 18;15:1329634. doi: 10.3389/fimmu.2024.1329634. eCollection 2024.
Immunotherapy based on immune checkpoint inhibitors (ICIs) has become the first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, only a small portion of patients are responsive to ICIs. It is important to identify the patients who are likely to benefit from ICIs in clinical practice. We aimed to examine the significance of serum IL-6 and CRP levels in predicting the effectiveness of ICIs for uHCC.
We retrospectively recruited 222 uHCC patients who received ICIs treatment (training cohort: 124 patients, validation cohort: 98 patients). In the training cohort, patients are categorized into the response group (R) and no-response group (NR). The levels of serum IL-6 and CRP were compared between the two groups. Internal validation was performed in the validation cohort. Survival analysis was carried out using the Kaplan-Meier method and Cox proportional hazard regression model. The nomograms were developed and assessed using the consistency index (C-index) and calibration curve.
Serum levels of IL-6 and CRP were significantly lower in the R group than in the NR group (9.94 vs. 36.85 pg/ml, p< 0.001; 9.90 vs. 24.50 mg/L, p< 0.001, respectively). An ROC curve was employed to identify the optimal cut-off values for IL-6 and CRP in both groups, resulting in values of 19.82 pg/ml and 15.50 mg/L, respectively. Multivariate Cox regression analysis revealed that MVI (HR 1.751, 95%CI 1.059-2.894, p=0.029; HR 1.530, 95%CI 0.955-2.451, p=0.077), elevated IL-6 (HR 1.624, 95%CI 1.016-2.596, p=0.043; HR 2.146, 95%CI 1.361-3.383, p =0.001) and high CRP (HR 1.709, 95%CI 1.041-2.807, p=0.034; HR 1.846, 95%CI 1.128-3.022, p = 0.015) were independent risk factors for PFS and OS, even after various confounders adjustments. Nomograms are well-structured and validated prognostic maps constructed from three variables, as MVI, IL6 and CRP.
Low levels of IL-6 and CRP have a positive correlation with efficacy for uHCC patients receiving ICIs.
免疫检查点抑制剂（ICIs）为基础的免疫疗法已成为不可切除肝细胞癌（uHCC）的一线治疗方法。然而，只有一小部分患者对 ICI 有反应。在临床实践中，识别可能从 ICI 中获益的患者非常重要。我们旨在研究血清 IL-6 和 CRP 水平在预测 uHCC 患者对 ICI 疗效中的意义。
我们回顾性招募了 222 例接受 ICI 治疗的 uHCC 患者（训练队列：124 例，验证队列：98 例）。在训练队列中，患者分为应答组（R）和无应答组（NR）。比较两组患者的血清 IL-6 和 CRP 水平。在验证队列中进行内部验证。使用 Kaplan-Meier 方法和 Cox 比例风险回归模型进行生存分析。使用一致性指数（C 指数）和校准曲线开发和评估列线图。
R 组血清 IL-6 和 CRP 水平明显低于 NR 组（9.94 比 36.85 pg/ml，p<0.001；9.90 比 24.50 mg/L，p<0.001）。ROC 曲线用于确定两组中 IL-6 和 CRP 的最佳截断值，分别为 19.82 pg/ml 和 15.50 mg/L。多变量 Cox 回归分析显示，MVI（HR 1.751，95%CI 1.059-2.894，p=0.029；HR 1.530，95%CI 0.955-2.451，p=0.077）、升高的 IL-6（HR 1.624，95%CI 1.016-2.596，p=0.043；HR 2.146，95%CI 1.361-3.383，p=0.001）和高 CRP（HR 1.709，95%CI 1.041-2.807，p=0.034；HR 1.846，95%CI 1.128-3.022，p=0.015）是 PFS 和 OS 的独立危险因素，即使在各种混杂因素调整后也是如此。列线图是基于三个变量（MVI、IL6 和 CRP）构建的结构良好且经过验证的预后图谱。
低水平的 IL-6 和 CRP 与接受 ICI 治疗的 uHCC 患者的疗效呈正相关。
