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

<div><p>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, <i>P</i> = 0.047). Subgroup analyses found that PD-L1 positive expression in TIICs indicated a better prognosis especially in breast cancer patients (HR = 0.359, <i>P</i> = 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, <i>P</i> = 0.001 and HR = 0.549, <i>P</i> = 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.</p></div

Flow diagram of the literature search and study selection for the meta-analysis.

<p>The flow diagram shows eligible publications at each stage of the analysis process. The database search was conducted in December 2016.</p

Forest plot of hazard ratios shows the associations between PD-L1 expression in TIICs and cancer prognosis.

<p>Forest plot of hazard ratios shows the associations between PD-L1 expression in TIICs and cancer prognosis.</p

Forest plot shows the associations between PD-L1 expression in TIICs and five year overall survival of cancer patients.

<p>Forest plot shows the associations between PD-L1 expression in TIICs and five year overall survival of cancer patients.</p

Subgroup analysis by different cutoff values shows the associations between PD-L1 expression in TIICs and five year overall survival of cancer patients.

<p>Subgroup analysis by different cutoff values shows the associations between PD-L1 expression in TIICs and five year overall survival of cancer patients.</p

Forest plot of hazard ratios form subgroup analysis by different cutoff values shows the associations between PD-L1 expression in TIICs and cancer prognosis.

<p>Forest plot of hazard ratios form subgroup analysis by different cutoff values shows the associations between PD-L1 expression in TIICs and cancer prognosis.</p

POMC/β-actin ratio,normalized to control, in hypothalamus and bran stem of fed and fasted mice.

<p>Con: control group; SR: SR 57227 (10 mg/kg, i.p.); On: ondansetron (3 mg/kg, i.p.). POMC: Pro-opiomelanocortin. Values are means ± SEM (n = 8–10). #, P < 0.05 vs. non-fasting control group; **, P < 0.01 vs. fasting control group.</p

Corticosterone and ACTH levels, normalized to control, in fed and fasted mice.

<p>Con: control group; SR: SR 57227 (10 mg/kg, i.p.); On: ondansetron (3 mg/kg, i.p.). Values are means ± SEM (n = 6 or 7).*, P < 0.05 vs. non-fasting control group.</p

TH/β-actin ratio,normalized to control, in hypothalamus and bran stem of fed and fasted mice.

<p>Con: control group; SR: SR 57227 (10 mg/kg, i.p.); On: ondansetron (3 mg/kg, i.p.). TH: tyrosine hydroxylase. Values are means ± SEM (n = 8–10). #, P < 0.05 vs. non-fasting control group; *, P < 0.05 vs. fasting control group.</p

Effects of acute SR 57227 on cumulative food intake in fed and fasted mice.

<p>SR: SR 57227 (1, 3 and 10 mg/kg, i.p.); On: ondansetron (3 mg/kg, i.p.). Values are means ± SEM (n = 8–10). #, P < 0.05; ##, P < 0.01 vs. non-fasting group; *, P <0.05; **, P < 0.01 vs. fasting group.</p