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Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis

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Abstract

Background

Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear.

Methods

We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs).

Results

A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74–3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47–3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55–2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36–2.49, P = 0.906).

Conclusion

sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

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Data availability

All data and material analyzed during this study are included in this article.

Abbreviations

APCs:

Antigen-presenting cells

CI:

Confidence interval

CTLA-4:

Cytotoxic T lymphocyte antigen 4

DCs:

Dendritic cells

DFS:

Disease-free survival

ELISA:

Enzyme-linked immunosorbent assay

ERK:

Extracellular-signal regulated kinase

GM-CDF:

Granulocyte–macrophage colony-stimulating factor

HR:

Hazard ratio

HCC:

Hepatocellular carcinoma

ICIs:

Immune checkpoint inhibitors

IFN:

Interferon

IL:

Interleukin

ITSM:

Immunoreceptor tyrosine-based switch motif

NK cells:

Natural killer cells

NKT cells:

Natural killer T cells

NOS:

Newcastle–ottawa scale

OS:

Overall survival

PD-1:

Programmed cell death-1

PD-L1:

Programmed cell death ligand-1

PLCγ2:

Phospholipase C-γ2

PI3K:

Phosphatidylinositol 3 kinase

RFS:

Recurrence-free survival

sPD-1:

Soluble programmed cell death-1

sPD-L1:

Soluble programmed cell death ligand-1

TACE:

Transcatheter arterial chemoembolization

TFS:

Tumor-free survival

TTP:

Time to progression

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Funding

This work was supported by the Taishan Scholars Program for Young Expert of Shandong Province (tsqn20161064), the National Natural Science Foundation of China (81874178 & 82073200), and founds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No.2020GXRC023).

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  1. Jun-shuai Xue and Hui Liu contributed equally to this paper.

Authors and Affiliations

  1. Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China

    Jun-shuai Xue, Hui Liu, Guang-Xiao Meng, Zi-Niu Ding, Lun-Jie Yan, Sheng-Yu Yao, Hai-Chao Li, Zhao-Ru Dong, Zhi-Qiang Chen, Jian-Guo Hong & Tao Li

  2. Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, 250012, China

    Tao Li

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Contributions

JSX and TL designed the study. JSX, HL, and ZRD performed the systematic search. JSX, HL, GXM, ZND, LJY, SYY, HCL, JGH, ZRD, and ZQC selected eligible articles and conducted the quality assessment. JSX and HL analyzed, interpreted the data, and drafted the manuscript. TL revised the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Tao Li.

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Xue, Js., Liu, H., Meng, GX. et al. Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis. Cancer Immunol Immunother 71, 1633–1644 (2022). https://doi.org/10.1007/s00262-021-03103-2

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