Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2019

01-03-2019 | Translational Research and Biomarkers

Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression

Authors: Tsunehiko Shigemori, MD, Yuji Toiyama, MD, PhD, FACS, Yoshinaga Okugawa, MD, PhD, Akira Yamamoto, MD, Chengzeng Yin, MD, Aya Narumi, MD, Takashi Ichikawa, MD, Shozo Ide, MD, PhD, Tadanobu Shimura, MD, PhD, Hiroyuki Fujikawa, MD, PhD, Hiromi Yasuda, MD, PhD, Junichiro Hiro, MD, PhD, Shigeyuki Yoshiyama, MD, PhD, Masaki Ohi, MD, PhD, Toshimitsu Araki, MD, PhD, Masato Kusunoki, MD, PhD

Published in: Annals of Surgical Oncology | Issue 3/2019

Login to get access

Abstract

Background

This study assessed programmed cell death ligand 1 (PD-L1) expression in primary tissues and soluble PD-L1 (sPD-L1) concentration in matched preoperative serum in gastric cancer (GC) patients to perform direct comparison between tissue and serum PD-L1 expression and to clarify the prognostic implication in GC.

Methods

The study enrolled 180 GC patients who underwent surgery for GC at the authors’ institution. The study evaluated tissue PD-L1 expression using immunohistochemistry and quantified sPD-L1 concentration in preoperative serum using enzyme-linked immunosorbent assay in GC patients.

Results

The findings showed that PD-L1 was overexpressed in GC tissues compared with normal mucosa. Tissue PD-L1 expression was significantly higher in the GC patients with advanced T stage, presence of lympho-vascular invasion, lymph node metastasis, and peritoneal metastasis. Furthermore, elevated tissue PD-L1 expression was significantly associated with poor prognosis for overall survival (OS) and disease-free survival (DFS). Serum sPD-L1 was significantly higher in the GC patients than in the healthy volunteers. Although serum sPD-L1 was not correlated with any clinicopathologic factors, the patients with high serum sPD-L1 showed poorer OS and DFS than those with low sPD-L1. Multivariate analyses showed that both elevated tissue PD-L1 and serum sPD-L1 were independent prognostic factors for poor OS [tissue PD-L1: hazard ratio (HR), 4.28; 95% confidence interval (CI), 1.43–12.8; P = 0.0094 vs. serum sPD-L1: HR, 11.2; 95% CI, 3.44–36.7; P = 0.0001] and poor DFS (tissue PD-L1: HR, 6.96; 95% CI, 2.48–19.6; P = 0.0002 vs. serum sPD-L1: HR, 8.7; 95% CI, 3.16–23.9; P < 0.0001) for the GC patients. Furthermore, infiltrative CD8- and Foxp3-positive T cells were significantly increased in the GC patients with elevated tissue PD-L1 expression.

Conclusion

Both serum sPD-L1 and tissue PD-L1 expression may serve as predictive biomarkers for recurrence and prognosis in GC patients.
Appendix
Available only for authorised users
Literature
1.
Kashihara H, Shimada M, Yoshikawa K, et al. Risk factors for recurrence of gastric cancer after curative laparoscopic gastrectomy. J Med Investig. 2017;64:79–84.CrossRef
2.
Marano L, Polom K, Patriti A, et al. Surgical management of advanced gastric cancer: an evolving issue. Eur J Surg Oncol. 2016;42:18–27.CrossRefPubMed
3.
4.
Vennin C, Murphy KJ, Morton JP, Cox TR, Pajic M, Timpson P. Reshaping the tumor stroma for treatment of pancreatic cancer. Gastroenterology. 2018;154:820–38.CrossRefPubMed
5.
6.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.CrossRefPubMed
7.
Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.CrossRefPubMed
8.
Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol. 2014;382:673–82.CrossRefPubMed
9.
10.
11.
Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390:1853–62.CrossRefPubMed
12.
Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefPubMed
13.
Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.CrossRefPubMed
14.
15.
Afreen S, Dermime S. The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. Hematol Oncol Stem Cell Ther. 2014;7:1–17.CrossRefPubMed
16.
Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother. 2005;54:307–14.CrossRefPubMed
17.
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.CrossRefPubMed
18.
Nomi T, Sho M, Akahori T, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007;13:2151–7.CrossRefPubMed
19.
Kim JW, Nam KH, Ahn SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016;19:42–52.CrossRefPubMed
20.
Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94:107–16.CrossRefPubMed
21.
Boland JM, Kwon ED, Harrington SM, et al. Tumor B7-H1 and B7-H3 expression in squamous cell carcinoma of the lung. Clin Lung Cancer. 2013;14:157–63.CrossRefPubMed
22.
Spranger S, Spaapen RM, Zha Y, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Translat Med. 2013;5:200ra116.CrossRef
23.
Thompson RH, Gillett MD, Cheville JC, et al. Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer. 2005;104:2084–91.CrossRefPubMed
24.
Chen Y, Wang Q, Shi B, et al. Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1 + cell lines. Cytokine. 2011;56:231–8.CrossRefPubMed
25.
Rossille D, Gressier M, Damotte D, et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial. Leukemia. 2014;28:2367–75.CrossRefPubMed
26.
Wang L, Wang H, Chen H, et al. Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma. Oncotarget. 2015;6:41228–36.PubMedPubMedCentral
27.
Mori K, Toiyama Y, Saigusa S, et al. Systemic analysis of predictive biomarkers for recurrence in colorectal cancer patients treated with curative surgery. Dig Dis Sci. 2015;60:2477–87.CrossRefPubMed
28.
Ha H, Nam AR, Bang JH, et al. Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy. Oncotarget. 2016;7:76604–12.PubMedPubMedCentral
29.
Lin G, Fan X, Zhu W, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8:83986–94.PubMedPubMedCentral
30.
Ceeraz S, Nowak EC, Noelle RJ. B7 family checkpoint regulators in immune regulation and disease. Trends Immunol. 2013;34:556–63.CrossRefPubMed
31.
32.
Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exper Med. 2009;206:3015–29.CrossRef
33.
He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2015;5:13110.CrossRefPubMedPubMedCentral
34.
Frigola X, Inman BA, Lohse CM, et al. Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin Cancer Res. 2011;17:1915–23.CrossRefPubMedPubMedCentral
35.
Tamura T, Ohira M, Tanaka H, et al. Programmed death-1 ligand-1 (pdl1) expression is associated with the prognosis of patients with stage II/III gastric cancer. Anticancer Res. 2015;35:5369–76.PubMed
36.
Zhang M, Dong Y, Liu H, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1901 patients. Sci Rep. 2016;6:37933.CrossRefPubMedPubMedCentral
37.
Brody R, Zhang Y, Ballas M, et al. PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer Amsterdam. 2017;112:200–15.CrossRef
38.
39.
Ju X, Shen R, Huang P, et al. Predictive relevance of PD-L1 expression with pre-existing TILs in gastric cancer. Oncotarget. 2017;8:99372–81.PubMedPubMedCentral
40.
Amatatsu M, Arigami T, Uenosono Y, et al. PD-L1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer. Cancer Sci. 2018;109:814–20.CrossRefPubMedPubMedCentral
41.
Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting SRC homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci USA. 2001;98:13866–71.CrossRefPubMedPubMedCentral
Metadata
Title
Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression
Authors
Tsunehiko Shigemori, MD
Yuji Toiyama, MD, PhD, FACS
Yoshinaga Okugawa, MD, PhD
Akira Yamamoto, MD
Chengzeng Yin, MD
Aya Narumi, MD
Takashi Ichikawa, MD
Shozo Ide, MD, PhD
Tadanobu Shimura, MD, PhD
Hiroyuki Fujikawa, MD, PhD
Hiromi Yasuda, MD, PhD
Junichiro Hiro, MD, PhD
Shigeyuki Yoshiyama, MD, PhD
Masaki Ohi, MD, PhD
Toshimitsu Araki, MD, PhD
Masato Kusunoki, MD, PhD
Publication date
01-03-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-07112-x

Other articles of this Issue 3/2019

Annals of Surgical Oncology 3/2019 Go to the issue

HEPATOBILIARY TUMORS

The Combination of APRI and ALBI Facilitates Preoperative Risk Stratification for Patients Undergoing Liver Surgery After Neoadjuvant Chemotherapy

Breast Oncology

OncotypeDX Recurrence Score Does Not Predict Nodal Burden in Clinically Node Negative Breast Cancer Patients

Thoracic Oncology

Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients

Gastrointestinal Oncology

Increased Expression of DNAJC12 is Associated with Aggressive Phenotype of Gastric Cancer

Gastrointestinal Oncology

Reply to: “Multimodal Treatment of Locally Advanced Gastric Cancer: Will the West Meet the East?”, by Marino, Elisabetta et al.

Reconstructive Oncology

Breast Reconstruction in an Underserved Population: A Retrospective Study