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阿替利珠单抗和贝伐单抗治疗的肝细胞癌中恶性细胞和浸润细胞联合PD-L1表达的预后意义

Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab.

作者信息

Lee Jaejun, Yoo Jae-Sung, Kim Ji Hoon, Lee Dong Yeup, Yang Keungmo, Kim Bohyun, Choi Joon-Il, Jang Jeong Won, Choi Jong Young, Yoon Seung Kew, Han Ji Won, Sung Pil Soo

机构信息

The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Republic of Korea, Seoul, Republic of Korea.

Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Republic of Korea, Seoul, Republic of Korea.

出版信息

Front Immunol. 2024 Dec 10;15:1506355. doi: 10.3389/fimmu.2024.1506355. eCollection 2024.

Abstract

BACKGROUND

Programmed death-ligand 1 (PD-L1) expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells.

METHODS

This study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023. PD-L1 expression on tumor tissues was assessed using the combined positive score (CPS) with cutoff values of 1 and 10, utilizing antibody clone 22C3 (Dako).

RESULTS

The distribution of PD-L1 CPS included 24 patients with CPS <1, 33 patients with CPS 1-10, and 15 patients with CPS ≥10. Significant differences in overall survival (OS) were observed across the three groups, with CPS ≥10 showing the highest survival rates (p = 0.010). Patients with CPS ≥10 had better OS than those with CPS <10 (median OS 14.8 vs. 8.3 months, P = 0.046), and CPS ≥1 had better OS than CPS <1 (P = 0.021). For progression-free survival (mPFS), the CPS ≥10 group had the highest median PFS of 11.0 months among the three groups (P = 0.044). Objective response rates (ORR) were higher in the PD-L1 CPS ≥10 group than in the 1-10 and <1 group (53.3%, 27.3%, and 16.7%, respectively; = .047). Multivariate analysis identified that PD-L1 expression ≥10 and ≥1 were associated with favorable outcomes regarding OS (hazard ratio [HR] 0.283, = .027 and HR 0.303, = .006, respectively).

CONCLUSIONS

Combined analysis of PD-L1 expression in malignant and tumor-infiltrating cells can be a promising biomarker for the prognosis of HCC patients treated with AB.

摘要

背景

程序性死亡配体1(PD-L1)不仅在恶性细胞中大量表达,在肝细胞癌(HCC)肿瘤微环境(TME)中的浸润细胞中也大量表达。本研究探讨了TME中PD-L1表达与接受阿替利珠单抗联合贝伐单抗(AB)治疗的HCC患者预后之间的关系,重点关注PD-L1在恶性细胞和肿瘤浸润细胞中的表达情况。

方法

本研究纳入了72例HCC患者,这些患者在2020年9月至2023年12月期间接受AB治疗前接受了经皮肝穿刺活检。使用抗体克隆22C3(Dako),采用联合阳性评分(CPS)评估肿瘤组织上的PD-L1表达,临界值分别为1和10。

结果

PD-L1 CPS的分布情况为:24例患者CPS<1,33例患者CPS为1-10,15例患者CPS≥10。三组患者的总生存期(OS)存在显著差异,CPS≥10组的生存率最高(p=0.010)。CPS≥10的患者的OS优于CPS<10的患者(中位OS为14.8个月对8.3个月,P=0.046),CPS≥1的患者的OS优于CPS<1的患者(P=0.021)。对于无进展生存期(mPFS),CPS≥10组在三组中的中位PFS最高,为11.0个月(P=0.044)。PD-L1 CPS≥10组的客观缓解率(ORR)高于1-10组和<1组(分别为53.3%、27.3%和16.7%;P=.047)。多因素分析确定,PD-L1表达≥10和≥1与OS的良好预后相关(风险比[HR]分别为0.283,P=.027和HR 0.303,P=.006)。

结论

对恶性细胞和肿瘤浸润细胞中PD-L1表达的联合分析可能是接受AB治疗的HCC患者预后的一个有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ef/11666515/005b1b9f7be1/fimmu-15-1506355-g001.jpg

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