循环免疫指标预测经乐伐替尼和免疫治疗的肝细胞癌患者的预后
Circulating immune index predicting the prognosis of patients with hepatocellular carcinoma treated with lenvatinib and immunotherapy.
作者信息
Guo De-Zhen, Zhang Shi-Yu, Dong San-Yuan, Yan Jia-Yan, Wang Yu-Peng, Cao Ya, Rao Sheng-Xiang, Fan Jia, Yang Xin-Rong, Huang Ao, Zhou Jian
机构信息
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
出版信息
Front Oncol. 2023 Feb 23;13:1109742. doi: 10.3389/fonc.2023.1109742. eCollection 2023.
BACKGROUND
Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy.
METHODS
A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×10/L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated.
RESULTS
Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII > 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; = 0.037) and disease control rate (89% vs 73%; = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not.
CONCLUSIONS
We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.
背景
基于免疫检查点抑制剂（ICI）的联合疗法为包括肝细胞癌（HCC）在内的多种恶性肿瘤的治疗开辟了一条新途径。然而，考虑到疗效不尽人意，迫切需要生物标志物来识别最有可能从基于ICI的联合疗法中获益的患者。
方法
回顾性纳入194例接受基于ICI的联合疗法治疗不可切除HCC的患者，并随机分为训练队列（n = 129）和验证队列（n = 65）。构建了一种新的循环免疫指数（CII），定义为白细胞计数（×10/L）与淋巴细胞比例（%）之比，并确定和验证了其预后价值。
结果
与CII>43.1的患者相比，CII≤43.1的患者总生存期（OS）延长（中位OS：24.7个月对15.1个月；6个月、12个月、18个月OS：94.2%、76.7%、66.1%对86.4%、68.2%、22.8%，P = 0.019），且CII被确定为OS的独立预后因素（风险比，2.24；95%置信区间，1.17 - 4.31；P = 0.015）。这些结果随后在验证队列中得到验证。此外，在汇总队列中，CII水平低的患者最佳放射学肿瘤反应（完全缓解、部分缓解、疾病稳定、疾病进展：3%、36%、50%、11%对0%、27%、46%、27%；P = 0.037）和疾病控制率（89%对73%；P = 0.031）有所改善，在新辅助队列中病理反应更好（病理完全缓解率、主要病理反应率、部分病理反应率、无病理反应率：20%、44%、28%、8%对0%、0%、40%、60%；P = 0.005）。淋巴细胞亚群检测显示，CD4 + T细胞比例升高与更好的OS相关，而CD8 + T细胞比例则不然。
结论
我们构建了一种新的循环免疫生物标志物，能够预测接受ICI和乐伐替尼联合治疗的HCC患者的OS和治疗疗效。
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