Skip to main content
Top
Published in: Medical Oncology 3/2011

01-09-2011 | Original Paper

High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation

Authors: Chuan-Yong Mu, Jian-An Huang, Ying Chen, Cheng Chen, Xue-Guang Zhang

Published in: Medical Oncology | Issue 3/2011

Login to get access

Abstract

The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling technique were performed to detect the expressions of PD-L1, CD1α, and CD83 on TIDC of 20 lung cancer tissues, and the expression of PD-L1 in CD1α+DCs and CD83+DCs and their significances were also explored. We found that the expression rate of PD-L1 in NSCLC was associated with histological types and overall survival. Patients with either adenocarcinoma or survival time after surgery less than 3 years showed higher expression rate of PD-L1. Furthermore, Cox model analysis indicated that PD-L1 might be regarded as a poor prognostic factor. PD-L1 could be also detected in CD1α+ immature DC in NSCLC, indicating that as a class of key anti-tumor immunocyte in tumor microenvironment, DC expressing PD-L1 itself might play an important role in keeping its immature status and contributing to tumor cells immune escape and disease progression.
Literature
1.
go back to reference Yasumoto K, Hanagiri T, Takenoyama M. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer. Gen Thorac Cardiovasc Surg. 2009;57:449–57.PubMedCrossRef Yasumoto K, Hanagiri T, Takenoyama M. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer. Gen Thorac Cardiovasc Surg. 2009;57:449–57.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference XU X, et al. Clinicopathological significance of major histocompatibility complex class I-related chain A and B expression in thyroid cancer. Clin Endocrinol. 2006;91:2704–12.CrossRef XU X, et al. Clinicopathological significance of major histocompatibility complex class I-related chain A and B expression in thyroid cancer. Clin Endocrinol. 2006;91:2704–12.CrossRef
4.
go back to reference Kaklamanis L, et al. Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am J Pathol. 1994;145:505–9.PubMed Kaklamanis L, et al. Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am J Pathol. 1994;145:505–9.PubMed
5.
go back to reference Blank C, Brown I, Peterson AC. PD-L1/B7–H1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+T cells. Cancer Res. 2004;64:1140–5.PubMedCrossRef Blank C, Brown I, Peterson AC. PD-L1/B7–H1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+T cells. Cancer Res. 2004;64:1140–5.PubMedCrossRef
6.
go back to reference Mary E, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. Exp Med. 2006;203:883–95.CrossRef Mary E, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. Exp Med. 2006;203:883–95.CrossRef
7.
go back to reference Fabienne H, et al. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood. 2008;112:2149–55.CrossRef Fabienne H, et al. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood. 2008;112:2149–55.CrossRef
8.
go back to reference Gabrilovich D. Mechanisms and functional significance of tumor-induced dendritic cell defects. Nat Rev Immunol. 2004;4:941–52.PubMedCrossRef Gabrilovich D. Mechanisms and functional significance of tumor-induced dendritic cell defects. Nat Rev Immunol. 2004;4:941–52.PubMedCrossRef
9.
go back to reference Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef
10.
go back to reference Olaussen KA, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.PubMedCrossRef Olaussen KA, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.PubMedCrossRef
11.
go back to reference Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9.PubMedCrossRef Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9.PubMedCrossRef
13.
go back to reference Chen C, et al. Expression of programmed-death receptor ligands 1 and 2 may contribute to the poor stimulatory potential of murine immature dendritic cells. Immunol. 2007;212:159–65. Chen C, et al. Expression of programmed-death receptor ligands 1 and 2 may contribute to the poor stimulatory potential of murine immature dendritic cells. Immunol. 2007;212:159–65.
14.
go back to reference Wong RM, et al. Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol. 2007;19:1223–34.PubMedCrossRef Wong RM, et al. Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol. 2007;19:1223–34.PubMedCrossRef
15.
go back to reference Tsushima F, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T cell anergy. Blood. 2007;110:180–5.PubMedCrossRef Tsushima F, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T cell anergy. Blood. 2007;110:180–5.PubMedCrossRef
16.
go back to reference Blank C, et al. Blockade of PD-L1 (B7–H1) augments human tumor-specific T cell responses in vitro. Int J Cancer. 2006;119:317–27.PubMedCrossRef Blank C, et al. Blockade of PD-L1 (B7–H1) augments human tumor-specific T cell responses in vitro. Int J Cancer. 2006;119:317–27.PubMedCrossRef
17.
go back to reference Brown JA, et al. Blockade of programmed death 1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170:1257–66.PubMed Brown JA, et al. Blockade of programmed death 1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170:1257–66.PubMed
18.
go back to reference Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.PubMed Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.PubMed
19.
go back to reference Matthias S. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocr Relat Cancer. 2006;13:779–95.CrossRef Matthias S. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocr Relat Cancer. 2006;13:779–95.CrossRef
20.
go back to reference Mary F, Barbara J. Dendritic cells: immune regulators in health and disease. Physiol Rev. 2002;82:97–130. Mary F, Barbara J. Dendritic cells: immune regulators in health and disease. Physiol Rev. 2002;82:97–130.
21.
go back to reference Zhou LJ, Thomas F. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. PNAS. 1996;93:2588–92.PubMedCrossRef Zhou LJ, Thomas F. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. PNAS. 1996;93:2588–92.PubMedCrossRef
22.
go back to reference Vakkila J, et al. A basis for distinguishing cultured dendritic cells and macrophages in cytospins and fixed sections. Pediatr Dev Pathol. 2005;8:43–51.PubMedCrossRef Vakkila J, et al. A basis for distinguishing cultured dendritic cells and macrophages in cytospins and fixed sections. Pediatr Dev Pathol. 2005;8:43–51.PubMedCrossRef
23.
go back to reference Ivan P, Dominique B, Nathalie F. Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage. Immunol. 2007;178:2763–9. Ivan P, Dominique B, Nathalie F. Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage. Immunol. 2007;178:2763–9.
24.
go back to reference Kim R, Emi M, Tanabe K. Functional roles of immature dendritic cells in impaired immunity of solid tumor and their targeted strategies for provoking tumor immunity. Clin Exp Immunol. 2006;146:189–96.PubMedCrossRef Kim R, Emi M, Tanabe K. Functional roles of immature dendritic cells in impaired immunity of solid tumor and their targeted strategies for provoking tumor immunity. Clin Exp Immunol. 2006;146:189–96.PubMedCrossRef
25.
go back to reference Hyun K, et al. Down-regulation of cellular vascular endothelial growth factor (VEGF) levels induces differentiation of leukemic cells into leukemic-dendritic cells in patients with acute myeloid leukemia. Blood ASH (Annual Meeting Abstracts). 2005;106: 2226. Hyun K, et al. Down-regulation of cellular vascular endothelial growth factor (VEGF) levels induces differentiation of leukemic cells into leukemic-dendritic cells in patients with acute myeloid leukemia. Blood ASH (Annual Meeting Abstracts). 2005;106: 2226.
26.
go back to reference Boorjian SA, et al. T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin Cancer Res. 2008;14:4800–8.PubMedCrossRef Boorjian SA, et al. T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin Cancer Res. 2008;14:4800–8.PubMedCrossRef
27.
go back to reference Sergey V, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008;112:1822–31.CrossRef Sergey V, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008;112:1822–31.CrossRef
28.
go back to reference Konishi J, et al. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor—infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res. 2004;10:5094–100.PubMedCrossRef Konishi J, et al. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor—infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res. 2004;10:5094–100.PubMedCrossRef
Metadata
Title
High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation
Authors
Chuan-Yong Mu
Jian-An Huang
Ying Chen
Cheng Chen
Xue-Guang Zhang
Publication date
01-09-2011
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2011
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9515-2

Other articles of this Issue 3/2011

Medical Oncology 3/2011 Go to the issue