Prognostic value of PD-L1 expression in tumor infiltrating immune cells in cancers: A meta-analysis.

Tiancheng Zhao,Yanhua Wu,Changfeng Li,Bin Zhang,Bingjin Li,Tifei Yuan

doi:10.1371/journal.pone.0176822

Abstract

Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy. It not only expressed in tumor cells (TCs) but also up regulated in tumor infiltrating immune cells (TIICs). Although the previous meta-analysis have shown that PD-L1 expression in TCs was a valuable biomarker in predicting cancer prognosis, but few researches systematic evaluated the association between its expression in TIICs and survival of cancer patients. Thus, we performed this meta-analysis to evaluate the prognostic value of PD-L1 expression in TIICs in different types of cancers. Our results are valuable supplements when using PD-L1 expression to predict the survival of cancer patients and to select the beneficial patients from PD-L1 target therapy. PubMed, Embase, Web of Science and the Cochrane Central Search Library were used to perform our systematic literature search. Overall survival (OS) at 5th years and hazard ratios (HRs) were calculated using random effects models. Eighteen studies involving 3674 patients were included. The median positive rate of PD-L1 staining in TIICs was 36.37%. PD-L1 positive expression in TIICs related to a lower risk of death (HR = 0.784, 95%CI: 0.616–0.997, P = 0.047). Subgroup analyses found that PD-L1 positive expression in TIICs indicated a better prognosis especially in breast cancer patients (HR = 0.359, P = 0.041). When using whole tissue section slides, or using ‘any expression in TIICs’ as a cutoff value to assessing the results of IHC staining, PD-L1 expression in TIICs had a good prognostic value in cancer prognosis (HR = 0.587, P = 0.001 and HR = 0.549, P = 0.002). Our findings suggested that PD-L1 expression in TIICs was related to a better survival of cancer. The comprehensive evaluation of tumor cells and tumor infiltrating immune cells are required when evaluating the effect of PD-L1 expression on prognosis of cancer in future research.

Highlights

Cancer remains the most prominent global health-related threat[1, 2]
Key words used included “programmed death-ligand 1 or PD-L1 or B7-H1 or CD274” and “tumor infiltrating lymphocyte or TIL or tumor infiltrating immune cells or TIIC or tumor infiltrating mononuclear cells or TIMC or tumor stroma” and “cancer or carcinoma or tumor” and “prognosis or survival”; the results were limited to human studies
The eligible studies were included in this meta-analysis based on the following criteria: (1) PD-L1 expression has been measured by immunohistochemistry (IHC) stain in tumor infiltrating immune cells rather than in tumor cells; (2) studies reported 5-year Overall survival (OS), hazard ratios (HRs) with 95%

Summary

Introduction

Cancer remains the most prominent global health-related threat[1, 2]. Traditional therapies such as tumorectomy, radiotherapy and chemotherapy are still the main treatments, but their efficacies are unsatisfactory in most cancers, especially in advanced cancers[3]. A meta-analysis including 20 trials reported that patients with positive PD-L1 expression might have a decreased risk of mortality compared to negative cases when treated with anti PD-1/PD-L1 antibodies[10]. The expression of PD-L1 linked to the response of immune checkpoint therapy and associated with the prognosis of several types of cancer, such as non-small-cell lung cancer[11], gastric cancer[12], and breast cancer[13]

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Discussion

Conclusion