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肿瘤浸润 CD8(+) T 细胞数量和血清 C 反应蛋白水平作为接受阿替利珠单抗联合贝伐珠单抗治疗的肝细胞癌患者的预后生物标志物

英文原题:Tumor-infiltrating CD8(+) T-cell numbers and serum C-reactive protein levels as a prognostic biomarker in hepatocellular carcinoma patients receiving atezolizumab plus bevacizumab.

PubMed 2025/01/08(内容时间) Hepatol Res Q2 · IF 3.7(JCR 2025)

研究概要

这些发现提示,CD8⁺ TIL 数量与血清 CRP 水平的组合可能作为预测阿替利珠单抗联合贝伐珠单抗在 HCC 患者中疗效的有用生物标志物。

中文摘要

目的:阿替利珠单抗联合贝伐珠单抗是不可切除肝细胞癌(HCC)的一线标准治疗。我们此前研究发现,CD8+TIL(肿瘤浸润淋巴细胞)可能是预测患者对此疗法应答的生物标志物。然而,并非所有存在CD8+ TIL的HCC患者都能从阿替利珠单抗和贝伐珠单抗治疗中获益。此外,多种癌症中,血清C反应蛋白(CRP)水平升高与接受免疫检查点抑制剂治疗后的不良结局相关。本研究旨在确定将CD8+ TIL数量与血清CRP水平联合使用,能否比单独采用CD8+ TIL数量更好地预测阿替利珠单抗和贝伐珠单抗治疗应答。方法:纳入46例提供肝活检样本的HCC患者,通过免疫组织化学测定肝组织中的CD8+ TIL数量。结果:13例患者(28.3%)同时具有较高CD8+ TIL数量和较低血清CRP水平(<0.54 mg/dL),该组治疗应答率最高。此外,与其余33例患者相比,该组中位总生存期和无进展生存期显著更长。多变量分析显示,CD8+ TIL数量高且CRP水平低(HR 0.264;P=0.037)及Child-Pugh A级(HR 0.277;P=0.009)均与总生存期改善相关。结论:这些发现提示,联合评估CD8+ TIL数量和血清CRP水平,可能成为预测HCC患者阿替利珠单抗联合贝伐珠单抗疗效的有用生物标志物。

展开英文摘要原文

AIM: Atezolizumab plus bevacizumab is an established first-line treatment for unresectable hepatocellular carcinoma (HCC). Our previous research identified CD8 + tumor-infiltrating lymphocytes (TILs) as a potential biomarker for predicting patient response to this therapy. However, not all HCC patients with CD8 + TILs respond favorably to atezolizumab and bevacizumab. Moreover, elevated serum C-reactive protein (CRP) levels have been associated with poor outcomes in patients treated with immune checkpoint inhibitors across various cancer types. The aim of this study was to determine whether CD8 + TIL numbers combined with serum CRP levels could collectively predict the response to atezolizumab and bevacizumab better than CD8 + TIL numbers alone. METHODS: A total of 46 HCC patients who provided liver biopsy samples were included. CD8 + TIL numbers in liver tissue were measured using immunohistochemistry. RESULTS: A group of 13 patients (28.3%) with high CD8 + TIL numbers and low ( 0.54 mg/dl) serum CRP levels demonstrated the highest treatment response rate. Furthermore, this group had a significantly longer median overall survival and progression-free survival than the remaining 33 patients. Multivariate analysis revealed that high CD8 + TIL numbers with low CRP levels (HR 0.264; p = 0.037) and Child-Pugh class A (HR 0.277; p = 0.009) were associated with improved overall survival. CONCLUSIONS: These findings suggest that the combination of CD8 + TIL numbers and serum CRP levels may serve as a useful biomarker for predicting the efficacy of atezolizumab plus bevacizumab in HCC patients.

论文信息

作者
Kuwano A、Yada M、Tanaka K、Takahira J、Suzuki H、Ohishi Y、Motomura K
单位
Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka, Japan.Japan
期刊
Hepatology research : the official journal of the Japan Society of Hepatology2025 Apr
原文标识
PubMed 40317802 · DOI 10.1111/hepr.14157