The prognostic value of PD-L1 expression for non-small cell lung cancer patients: A meta-analysis

doi:10.1016/j.ejso.2015.01.020

European Journal of Surgical Oncology (EJSO)

Volume 41, Issue 4, April 2015, Pages 450-456

https://doi.org/10.1016/j.ejso.2015.01.020 Get rights and content

Abstract

Background

A meta-analysis was conducted to investigate the much-debated relationship between the gene expression of programmed cell death-ligand 1 (PD-L1) and cancer patient prognosis. The prognostic value of measuring PD-L1 expression in non-small cell lung cancer (NSCLC) patients was analyzed.

Methods

We searched PubMed for studies about the relationship between PD-L1 expression and NSCLC patient prognosis. Only studies with patient survival data related to PD-L1 expression in NSCLC patients with different characteristics were included. The effect size (ES) for this analysis was the hazard ratio (HR) with 95% confidence intervals (CI) for overall survival (OS).

Results

Six studies with 1157 patients were included with the defined including and excluding criteria. There is no significant heterogeneity among the studies (I² = 0%, p = 0.683). PD-L1 expression was significantly associated with the differentiation of tumor (poor vs. well: OR = 1.91, 95% CI: 1.33–2.75, p = 0.001). High PD-L1 expression was also correlated with poor prognosis in terms of the OS of patients with NSCLC (pooled HR = 1.75, 95% CI: 140–2.20, p < 0.001; heterogeneity test: I² = 0%, p = 0.643).

Conclusions

NSCLC patients with positive PD-L1 expression exhibited poor OS. The PD-L1 expression was higher in tumors with poor differentiation.

Introduction

Lung cancer is the most common cause of cancer death, and is the most commonly diagnosed cancer in men and the fourth most commonly diagnosed cancer in women.¹ In China between 1990 and 2010, the death rate due to cancer went from the 13th to the 5th most common cause of death.² Approximately 85% of patients with lung cancer are diagnosed with non-small cell lung cancer (NSCLC) and 80% of lung cancer were diagnosed with late stage.3, 4 The survival rate and prognosis of patients with late stage NSCLC is extremely low.⁵

The development of cancer is a complex progress in which, T cells in the host's antitumor immune system play an important role. To evade recognition by the host's immune system, cancer cells can induce T cell non-responsiveness by expressing certain ligands which act on specific immune checkpoint pathways such as programmed cell death-1pathway.6, 7 In 1999, the first duplication of programmed cell death-1 (PD-1) (B7-H1) was created based on its DNA sequence.⁸ PD-1, an immune checkpoint which is expressed on the surface of T, B and NK cells, is a surface-receptor member of the B7-CD28 superfamily.6, 9 The key role of the PD-1 pathway plays in blunting the T cell immune function was confirmed for the first time in PD-1 knockout mice.¹⁰ Cells that express PD-1 evade T cell immunity via mechanisms such as exhaustion, apoptosis and anergy, and thereby defend tumor cells from cytolysis.¹¹ Programmed cell death-ligand 1, the major ligand for PD-1, is a cell surface protein in the B7 family which is found in tumor specimens from NSCLC patients.6, 12

In recent years, PD-L1 expression has been studied in several cancers, including breast, gastric, pancreatic, ovarian cancer, renal cell carcinoma, melanoma and glioblastoma.13, 14, 15, 16, 17, 18, 19 And the overexpression of PD-L1 indicated better prognosis in glioblastoma patients, yet the opposite result of PD-L1 was reported in gastric cancer.15, 19 In addition, the predictive role of PD-L1 for anti-PD-1/PD-L1 immunotherapy in cancer patients has raised people's attention.20, 21 The association between abnormal PD-L1 expression and NSCLC survival has also been investigated. The prognostic value of PD-L1 expression remains controversial.6, 22, 23, 24, 25, 26 Because some studies of PD-L1 expression have relied on relatively small sample sizes with limited statistical power, it is necessary to assess the possible association between PD-L1 and the prognosis for NSCLC patients using an up-to-date meta-analysis.

Section snippets

Search strategy

Relevant studies in English were searched in the database of PubMed with the following terms: “Programmed cell death-ligand 1”, “PD-L1”, “B7-H1” and “lung cancer”. The last search was conducted on August 26, 2014. If necessary we also searched the Cochrane Library. When the same patients were included in different publications, the most recent study was used for analysis.

Inclusion and exclusion criteria

Qualified studies were gathered in accordance with the following inclusion criteria: (1) the histology type of cancer was

Characteristics of studies

After the initial search of PubMed, 93 relevant records were found. Due to studies about other cancers or subjects irrelevant to this meta-analysis, 75 records were excluded based on the title or abstract. Eighteen possible full text studies were carefully reviewed. 12 studies were then excluded for the following reasons: 5 for insufficient survival data, 3 because the articles were not written in English, and 4 because the study was based on cell lines. As a result, 6 studies involving 1157

Discussion

Using a meta-analysis, we assessed the potential role of PD-L1 expression in predicting OS in NSCLC patients. The results of our analysis show that positive PD-L1 expression is correlated with poor prognosis in NSCLC patients. The analysis found no significant relationship between PD-L1 expression and clinical features, including gender, histology, smoking status, tumor stage, and the presence or absence of lymph node metastasis. However, the pooled analysis showed that poor tumor

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^f: These authors contributed equally to this work.

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ReviewThe prognostic value of PD-L1 expression for non-small cell lung cancer patients: A meta-analysis

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Search strategy

Inclusion and exclusion criteria

Characteristics of studies

Discussion

Lancet

Eur J Cancer

Crit Rev Oncol Hematol

Lab Invest

Ann Oncol

J Thorac Cardiovasc Surg

Lancet Oncol

Blood

Global cancer statistics

CA Cancer J Clin

Current status of targeted therapy in non-small cell lung cancer

Drugs Today (Barc)

Cancer treatment and survivorship statistics, 2012

CA Cancer J Clin

The world health report 2002 – reducing risks, promoting healthy life

Educ Health (Abingdon)

Emerging immunotherapies in the treatment of Non-Small Cell Lung Cancer (NSCLC): the role of immune checkpoint inhibitors

Am J Clin Oncol

B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion

Nat Med

Update on immune checkpoint inhibitors in lung cancer

Cancer Control

Expression of programmed death 1 ligands by murine T cells and APC

J Immunol

Inhibitory B7-family molecules in the tumour microenvironment

Nat Rev Immunol

The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

J Hematol Oncol

PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer

Hepatogastroenterology

PD-L1 expression in triple-negative breast cancer

Cancer Immunol Res

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications

Chin J Cancer Res

Review
The prognostic value of PD-L1 expression for non-small cell lung cancer patients: A meta-analysis