{"title":"Tumor-infiltrating CD8+ T-cell numbers and serum C-reactive protein levels as a prognostic biomarker in hepatocellular carcinoma patients receiving atezolizumab plus bevacizumab","authors":"Akifumi Kuwano, Masayoshi Yada, Kosuke Tanaka, Junro Takahira, Hideo Suzuki, Yoshihiro Ohishi, Kenta Motomura","doi":"10.1111/hepr.14157","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>Atezolizumab plus bevacizumab is an established first-line treatment for unresectable hepatocellular carcinoma (HCC). Our previous research identified CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) as a potential biomarker for predicting patient response to this therapy. However, not all HCC patients with CD8<sup>+</sup> 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<sup>+</sup> TIL numbers combined with serum CRP levels could collectively predict the response to atezolizumab and bevacizumab better than CD8<sup>+</sup> TIL numbers alone.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A total of 46 HCC patients who provided liver biopsy samples were included. CD8<sup>+</sup> TIL numbers in liver tissue were measured using immunohistochemistry.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A group of 13 patients (28.3%) with high CD8<sup>+</sup> 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<sup>+</sup> TIL numbers with low CRP levels (HR 0.264; <i>p</i> = 0.037) and Child–Pugh class A (HR 0.277; <i>p</i> = 0.009) were associated with improved overall survival.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings suggest that the combination of CD8<sup>+</sup> TIL numbers and serum CRP levels may serve as a useful biomarker for predicting the efficacy of atezolizumab plus bevacizumab in HCC patients.</p>\n </section>\n </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"600-610"},"PeriodicalIF":3.9000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hepr.14157","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的 阿特珠单抗联合贝伐单抗是治疗不可切除肝细胞癌(HCC)的成熟一线疗法。我们之前的研究发现,CD8+肿瘤浸润淋巴细胞(TILs)是预测患者对该疗法反应的潜在生物标志物。然而,并非所有具有 CD8+ TILs 的 HCC 患者都能对阿特珠单抗和贝伐珠单抗产生良好反应。此外,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的各种癌症患者的不良预后有关。本研究旨在确定 CD8+ TIL 数量与血清 CRP 水平相结合是否比单独的 CD8+ TIL 数量更能预测对阿特珠单抗和贝伐珠单抗的反应。 方法 共纳入 46 名提供肝活检样本的 HCC 患者。采用免疫组化方法测量肝组织中的 CD8+ TIL 数量。 结果 CD8+ TIL 数量高且血清 CRP 水平低(≤0.54 mg/dl)的 13 例患者(28.3%)的治疗反应率最高。此外,这组患者的中位总生存期和无进展生存期明显长于其余33名患者。多变量分析显示,CD8+ TIL 数量高、CRP 水平低(HR 0.264;p = 0.037)和 Child-Pugh 分级 A(HR 0.277;p = 0.009)与总生存期的改善相关。 结论 这些研究结果表明,CD8+ TIL 数量和血清 CRP 水平的组合可作为预测阿特珠单抗加贝伐单抗对 HCC 患者疗效的有用生物标志物。
Tumor-infiltrating CD8+ T-cell numbers and serum C-reactive protein levels as a prognostic biomarker in hepatocellular carcinoma patients receiving atezolizumab plus bevacizumab
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.
期刊介绍:
Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.