High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer

Okuma, Yusuke; Hosomi, Yukio; Nakahara, Yoshiaki; Watanabe, Kageaki; Sagawa, Yukiko; Homma, Sadamu

doi:10.1016/j.lungcan.2016.11.023

Cited by 154 publications

(166 citation statements)

References 38 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…An increasing number of studies have reported that sPD-1 and sPD-L1 might play crucial roles in the prediction of treatment responses and prognosis in cancer patients [19–21]. However, the regulation, source and prognostic value of sPD-1/sPD-L1, as well as their association with clinicopathological factors in HCC, remain matters of debate.…”

Section: Discussionmentioning

confidence: 99%

“…In multivariable analysis using a Cox regression model, we found that sPD-L1 was a negative independent prognostic factor [Hazard Ratio (HR) for DFS 2.58 (1.14–5.84), P = 0.023; HR for OS 1.77 (1.01–3.12), P = 0.048] in accordance with a recent study [14], while sPD-1 was a favorable independent prognostic factor [HR for DFS 0.32 (0.14–0.74), P = 0.007; HR for OS: 0.54 (0.30–0.98), P = 0.044] in HCC. For other malignancies, such as lung cancer [19] and diffuse large B-cell lymphoma [9], several reports have also demonstrated that sPD-L1 is an unfavorable prognostic biomarker. Regarding sPD-1, an elevated sPD-1 level was associated with prolonged OS ( P = 0.006) and progression-free survival ( P = 0.013) for patients with non-small cell lung cancer undergoing erlotinib therapy [12].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

Chang

Huang

Wei

et al. 2018

Cancer Immunol Immunother

105

104

View full text Add to dashboard Cite

BackgroundBlocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients.MethodsThis study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs.ResultsThe best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14–5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01–3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14–0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30–0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined.ConclusionsOur findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients.Electronic supplementary materialThe online version of this article (10.1007/s00262-018-2271-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

Chang

Huang

Wei

et al. 2018

Cancer Immunol Immunother

105

104

View full text Add to dashboard Cite

show abstract

“…It has been further suggested that upregulation of sPD-L1 production is associated with tumor-inspired immune suppression and the poor prognosis [56–58]. In another study of 96 patients with lung cancer (85 NSCLC, 7 SCLC), sPD-L1 was detected by ELISA [59]. High sPD-L1 levels (≥7.32 ng/ml) were associated with poor prognosis (high vs low sPD-L1: OS 13.0 vs 20.4 months, p = 0.037) in these patients [59].…”

Section: Clinical Implications Of Soluble Pd-l1mentioning

confidence: 99%

“…In another study of 96 patients with lung cancer (85 NSCLC, 7 SCLC), sPD-L1 was detected by ELISA [59]. High sPD-L1 levels (≥7.32 ng/ml) were associated with poor prognosis (high vs low sPD-L1: OS 13.0 vs 20.4 months, p = 0.037) in these patients [59]. It remains unclear whether sPD-L1 level has correlation with clinical response to the checkpoint inhibitor treatment.…”

Section: Clinical Implications Of Soluble Pd-l1mentioning

confidence: 99%

Clinical applications of PD-L1 bioassays for cancer immunotherapy

2017

View full text Add to dashboard Cite

Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes of anti-PD-1/PD-L1 immunotherapy.

show abstract

“…PD-L1 expression by tumor cells is associated with worse prognosis for patients with many types of tumor, such as kidney cancer [4]. Patients with higher levels of soluble PD-L1 detected in peripheral blood have worse clinical outcomes in both solid and hematologic malignancies, including kidney, lung, and hepatocellular carcinoma, as well as myeloma and diffuse large B cell lymphoma [5–9]. Whether soluble PD-L1 in patients is a surrogate for expression of PD-L1 by the tumor, be it tumor cells or the infiltrating immune cells, or a measure of immunosuppressive peripheral blood cells is not well established across tumor types.…”

Section: Introductionmentioning

confidence: 99%

A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression

Mahoney

Shukla

Patsoukis

et al. 2018

Cancer Immunol Immunother

108

100

View full text Add to dashboard Cite

Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma. PD-L1 is a co-inhibitory molecule whose expression on the surface of tumor cells is associated with worse prognosis in many tumors. Here we describe a splice variant (secPD-L1) that does not splice into the transmembrane domain, but instead produces a secreted form of PD-L1 that has a unique 18 amino acid tail containing a cysteine that allows it to homodimerize and more effectively inhibit lymphocyte function than monomeric soluble PD-L1. We show that recombinant secPD-L1 can dimerize and inhibit T-cell proliferation and IFN-gamma production in vitro. The secPD-L1 variant is expressed by malignant cells in vitro that also express high levels of full-length PD-L1. Transcriptomic analysis of gene expression across The Cancer Genome Atlas found the strongest association of secPD-L1 with full-length PD-L1, but also with subsets of immunologic genes, such as in myeloid-derived suppressor cells. Moreover, the splice variant is also expressed in normal tissues and within normal peripheral blood cells it is preferentially expressed in activated myeloid cells. This is the first report of a form of secreted PD-L1 that homodimerizes and is functionally active. SecPD-L1 may function as a paracrine negative immune regulator within the tumor, since secPD-L1 does not require a cell-to-cell interaction to mediate its inhibitory effect.Electronic supplementary materialThe online version of this article (10.1007/s00262-018-2282-1) contains supplementary material, which is available to authorized users.

show abstract

High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer

Cited by 154 publications

References 38 publications

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

Clinical applications of PD-L1 bioassays for cancer immunotherapy

A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression

Contact Info

Product

Resources

About