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Meta-Analysis
. 2022 Nov 21;23(22):14496.
doi: 10.3390/ijms232214496.

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis

Fabio Scirocchi  1 , Lidia Strigari  2 , Alessandra Di Filippo  1 , Chiara Napoletano  1 , Angelica Pace  1 , Hassan Rahimi  1 , Andrea Botticelli  3 , Aurelia Rughetti  1 , Marianna Nuti  1 , Ilaria Grazia Zizzari  1
Affiliations
Meta-Analysis

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis

Fabio Scirocchi et al. Int J Mol Sci. .

Abstract

Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan−Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09−3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27−3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.

Keywords: immunotherapy; meta-analysis; prognostic biomarker; programmed death ligand-1 (PD-L1); solid cancer; soluble forms of IC receptors; soluble programmed death ligand-1 (sPD-L1); survival.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flow chart of the study selection process.
Figure 2
Figure 2
Overall pooled HRs comparing the high- versus the low-PD-L1 values group for OS in patients with solid cancer treated with immunotherapy. The column study indicates the reference (from which we extracted or calculated the HR and 95% CI) and the investigated tumor type [18,20,22,23,24,25,26,27,28].
Figure 3
Figure 3
Overall pooled HRs comparing the high- versus the low-PD-L1 values group for PFS in patients with solid cancer treated with immunotherapy. The column study indicates the reference (from which we extracted or calculated the HR and 95% CI) and the investigated tumor type [18,19,20,21,22,23,24,25,26,27,28,29].
Figure 4
Figure 4
Overall pooled HRs comparing the high- versus the low-PD-L1 values group for OS in NSCLC patients treated with immunotherapy. The column study indicates the reference (from which we extracted or calculated the HR and 95% CI) and the investigated tumor type [22,23,25,26,27].
Figure 5
Figure 5
Overall pooled HRs comparing the high- versus the low-PD-L1 values group for PFS in NSCLC patients treated with immunotherapy. The column study indicates the reference (from which we extracted or calculated the HR and 95% CI) and the investigated tumor type [21,22,23,24,25,26,27].
Figure 6
Figure 6
Schematic representation of sPD-L1 expression. Soluble forms of PD-L1 can be released by tumor cells or APCs in different ways: cleaved, secreted monomeric or dimeric splice variants or associated with microvesicles or exosomes. These soluble forms can be detected in serum/plasma. At baseline, before starting immunotherapy treatment, the concentration of sPD-L1 in blood of cancer patient could be a prognostic biomarker related to survival; high levels of sPD-L1 are associated with unfavorable OS and PFS. Created with BioRender.com, accessed on 20 July 2022.
See this image and copyright information in PMC

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