Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis

Li, Xiaosong; Li, Junwei; Li, Hui; Jiang, Tao

doi:10.1042/bsr20200459

Cited by 37 publications

(34 citation statements)

References 39 publications

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“…Like other studies, we observed that tumours with neoplastic and/or inflammatory cells expressing PD‐L1 showed pathological markers of aggressiveness (e.g. microvascular invasion and an inverse association with well‐differentiated tumours) 12,37 . Moreover, in univariate analysis, a high CD8+/CD3+ intratumoral lymphocyte ratio was significantly associated with longer OS.…”

Section: Discussionsupporting

confidence: 83%

Transarterial chemoembolisation enhances programmed death‐1 and programmed death‐ligand 1 expression in hepatocellular carcinoma

et al. 2021

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Aims Immunotherapies represent a new alternative therapeutic approach for hepatocellular carcinomas (HCCs), and have shown promising results when used in combination therapy. The aim of this study was to evaluate the potential of transarterial chemoembolisation (TACE) to modulate programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) expression profiles in a cohort of surgically treated HCCs. Methods and results A total of 82 surgically treated HCCs from patients who had undergone (n = 32) or not undergone (n = 50) preoperative TACE were included in the study. Immunohistochemical expression of PD‐1 and of PD‐L1 were analysed and compared according to TACE treatment. Pretreatment biopsies, which were available for 30 cases (20 with TACE and 10 without), were similarly analysed. Follow‐up data were retrieved from patients' charts. PD‐1 expression (≥1%) in intratumoral inflammatory cells (ICs) was observed in 46% of HCCs, and PD‐L1 expression (≥1%) in ICs and PD‐L1 expression in tumour cells (TCs) were observed in 46% and 16% of HCCs, respectively. A low level of PD‐1 expression (<1%) was associated with strong and diffuse glutamine synthetase overexpression (8% versus 27%, P = 0.024). HCCs from patients with TACE pretreatment showed significantly higher PD‐L1 expression in TCs than those from patients without TACE pretreatment (2% versus 0.4%, P = 0.027). PD‐1 expression in ICs and PD‐L1 expression in both ICs and TCs were higher in TACE‐resected tumours than in corresponding pre‐TACE biopsies (respectively: 1.8% versus 8.1%, P = 0.034; 0.8% versus 7.1%, P = 0.032; and 0% versus 2.4%, P = 0.043). Conclusion Our results, showing increases in PD‐1 expression and PD‐L1 expression in HCCs following TACE, support the use of TACE in combination with immunotherapy in selected cases to optimise tumour response.

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Section: Discussionsupporting

confidence: 83%

Transarterial chemoembolisation enhances programmed death‐1 and programmed death‐ligand 1 expression in hepatocellular carcinoma

et al. 2021

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“…Many recent meta-analyses have also demonstrated the prognostic value of PD-L1 expression in solid tumors. 12 , 13 , 56 , 57 Zeng et al showed that PD-L1 expression was associated with the prognosis of diffuse large B-cell lymphoma (DLBCL) (HR = 1.70, 95% CI = 1.05–2.74, p = 0.031). 56 Li et al reported that a high PD-L1 expression was associated with a shorter OS period of patients with hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“… 56 Li et al reported that a high PD-L1 expression was associated with a shorter OS period of patients with hepatocellular carcinoma. 13 In addition, a recent meta-analysis indicated that PD-L1 overexpression could predict poor survival outcomes related to bladder cancer. 58 Through our meta-analysis, we found a significant prognostic value of PD-L1 overexpression for poor OS, but not for PFS.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Jin¹,

Xie³

et al. 2020

Ther Adv Med Oncol

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Background: The prognostic value of programmed death-ligand 1 (PD-L1) expression in patients with malignant pleural mesothelioma (MPM) has been controversial according to previous investigations. Therefore, we conducted a meta-analysis to assess the potential prognostic significance of PD-L1 expression in MPM. Methods: PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were thoroughly searched for relevant original articles published before 9 April 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were calculated. The results of the meta-analysis were verified using The Cancer Genome Atlas (TCGA) dataset. Results: In total 16 studies were included in our meta-analysis. A high PD-L1 expression was associated with a poor OS (HR = 1.53, 95% CI = 1.28–1.83, p < 0.001), but not a grave PFS (HR = 1.07, 95% CI = 0.82–1.39, p = 0.643) in MPM. Furthermore, the PD-L1 expression correlated with the sarcomatoid + biphasic type of MPM (odds ratio = 4.32, 95% CI = 2.16–8.64, p < 0.001). TCGA data indicated that PD-L1 was a significant prognostic factor for OS (HR = 2.069, 95% CI = 1.136–3.769, p = 0.0175), but not for PFS (HR = 1.205, 95% CI = 0.572–2.539, p = 0.624), which was in accordance with the results of the meta-analysis. Conclusion: A high PD-L1 expression is a significant prognostic factor for poor OS of patients with MPM. We therefore suggest that PD-L1 expression levels can be used to predict the clinical outcomes of patients with MPM in the future.

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“…In most cases, the level of circulating sPD-L1 was found to be enhanced in the plasma of patients with the indicated pathology compared to healthy control (see Table 1 . For the oncology indications, the presence of sPD-L1 and its significance are discussed in the following studies: AEC [ 41 ]; BTC [ 42 , 43 ]; brain tumors [ 26 , 44 ]; CRCC [ 45 , 46 ]; CRC [ 47 ]; cutaneous melanoma [ 48 ]; DLBCL [ 49 , 50 ]; EOC [ 51 , 52 ]; ENKTL [ 53 , 54 ]; HNSCC [ 36 ]; HCC [ 55 , 56 , 57 ]; HL [ 54 , 58 ]; mesothelioma [ 59 , 60 ]; NC [ 61 , 62 ]; PGC [ 63 , 64 , 65 ]; NSCLC [ 66 , 67 ]; PC [ 68 ]; PCNSL [ 50 ]; STS [ 69 , 70 ]; TC [ 71 ]; TNBC [ 72 ]; WM [ 73 ].…”

Section: The Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.

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Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis

Cited by 37 publications

References 39 publications

Transarterial chemoembolisation enhances programmed death‐1 and programmed death‐ligand 1 expression in hepatocellular carcinoma

Transarterial chemoembolisation enhances programmed death‐1 and programmed death‐ligand 1 expression in hepatocellular carcinoma

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

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