Evaluation of PD-L1 as a Biomarker for Immunotherapy for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Zhou, Xueyin; Cao, Jiasheng; Topatana, Win; Xie, Tian-Ao; Chen, Tian'en; Hu, Jiahao; Li, Shijie; Juengpanich, Sarun; Lu, Ziyi; Zhang, Bin; Wang, Kaitai; Feng, Xiao; Shen, Jiliang; Chen, Mingyu

doi:10.2217/imt-2022-0168

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…A phase II clinical trial of pembrolizumab in patients with unresectable advanced HCC suggested that there was no significant correlation between PD-L1 positivity and treatment response [ 35 ]. However, Zhou et al reported a meta-analysis study showing that positive PD-L1 expression is better associated with ORR in patients with advanced liver cancer treated with anti-PD-1/PD-L1 [ 36 ]. Therefore, the expression of PD-L1 is currently controversial in predicting the efficacy of HCC.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials

Huang

Cui

et al. 2023

BMC Cancer

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Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV) infection. We conducted a meta-analysis to estimate the efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the first-line treatment of the unresectable HCC and to evaluate the benefits of different geographic regions and etiology stratifications. Methods Randomized clinical trials published up to 12th November 2022 were searched by online databases. Moreover, effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted from included studies. Pooled odds ratio (OR) and 95% CI for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated. Results A total of 3057 patients from five phase III randomized clinical trials were collected and reviewed for this meta-analysis. The pooled HR of OS (HR = 0.71; 95% CI: 0.60–0.85) and PFS (HR = 0.64; 95% CI: 0.53–0.77) demonstrated significantly better benefit in PD-1/PD-L1 inhibitors combination group than targeted monotherapy to treat unresectable HCC. In addition, combination therapy showed better ORR and DCR, with ORs of 3.29 (95% CI: 1.92–5.62) and 1.88 (95% CI: 1.35–2.61), respectively. The subgroup analysis indicated that PD-1/PD-L1 inhibitors combination therapy was significantly superior to anti-angiogenic monotherapy for HBV-related HCC in terms of OS (HR = 0.64; 95% CI: 0.55–0.74) and PFS (HR = 0.53; 95% CI:0.47–0.59), while there was no significant difference in patients with HCV (OS, HR = 0.81, p = 0.1) or non-viral (OS, HR = 0.91, p = 0.37; PFS, HR = 0.77, p = 0.05). Conclusions Meta-analysis revealed for the first-time that PD-1/PD-L1 inhibitors combination therapy for unresectable HCC was associated with better clinical outcomes than anti-angiogenic monotherapy, especially for HBV infection and Asian population.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials

Huang

Cui

et al. 2023

BMC Cancer

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“…A recent meta-analysis suggested that higher PD-L1 expression levels on tumor cells and tumor proportion score were associated with a higher ORR in HCC patients treated with ICIs (73). Another meta-analysis confirmed improved ORR in PD-L1-positive patients compared to PD-L1-negative patients (26% vs. 18%, OR=1.86).…”

Section: Pd-l1mentioning

confidence: 96%

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

Qin,

Jin,

2023

Front. Immunol.

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In recent years, immune checkpoint inhibitors (ICIs) have emerged as a transformative approach in treating advanced hepatocellular carcinoma (HCC). Despite their success, challenges persist, including concerns about their effectiveness, treatment costs, frequent occurrence of treatment-related adverse events, and tumor hyperprogression. Therefore, it is imperative to identify indicators capable of predicting the efficacy of ICIs treatment, enabling optimal patient selection to maximize clinical benefits while minimizing unnecessary toxic side effects and economic losses. This review paper categorizes prognostic biomarkers of ICIs treatment into the following categories: biochemical and cytological indicators, tumor-related markers, imaging and personal features, etiology, gut microbiome, and immune-related adverse events (irAEs). By organizing these indicators systematically, we aim to guide biomarker exploration and inform clinical treatment decisions.

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“… 244 Using meta‐analysis, Zhou et al. 245 discovered that high expression of PDL1 in tumor cells instead of tumor tissues was associated with better prognosis, and PDL1 could be used as a prognostic biomarker of immunotherapy efficacy for HCC.…”

Section: Cancer Immunotherapy: Inhibitor Applications Clinical Trials...mentioning

confidence: 99%

“…A recent study showed that the expression of PDL1, B7‐H3 and VISTA as well as some tumor necrosis factor receptor superfamily such as OX40L, CD27, 4‐1BB, CD40, and CD95/Fas were correlated with the head and neck squamous cell carcinoma immunotherapy efficiency, and could serve as potential biomarkers to predict the immunotherapy response 244 . Using meta‐analysis, Zhou et al 245 . discovered that high expression of PDL1 in tumor cells instead of tumor tissues was associated with better prognosis, and PDL1 could be used as a prognostic biomarker of immunotherapy efficacy for HCC.…”

Section: Cancer Immunotherapy: Inhibitor Applications Clinical Trials...mentioning

confidence: 99%

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

Qin,

Xie,

Wang

et al. 2024

MedComm

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Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety. However, only few tumor patients respond to immunotherapy and due to the complex and variable characters of cancer immune escape, the behavior and regulatory mechanisms of immune cells need to be deeply explored from more dimensions. Epigenetic modifications, metabolic modulation, and cell‐to‐cell communication are key factors in immune cell adaptation and response to the complex tumor microenvironment. They collectively determine the state and function of immune cells through modulating gene expression, changing in energy and nutrient demands. In addition, immune cells engage in complex communication networks with other immune components, which are mediated by exosomes, cytokines, and chemokines, and are pivotal in shaping the tumor progression and therapeutic response. Understanding the interactions and combined effects of such multidimensions mechanisms in immune cell modulation is important for revealing the mechanisms of immunotherapy failure and developing new therapeutic targets and strategies.

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Evaluation of PD-L1 as a Biomarker for Immunotherapy for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Cited by 6 publications

References 47 publications

Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials

Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

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