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.
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References
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.
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.
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.
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.
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.
Mary E, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. Exp Med. 2006;203:883–95.
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.
Gabrilovich D. Mechanisms and functional significance of tumor-induced dendritic cell defects. Nat Rev Immunol. 2004;4:941–52.
Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.
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.
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.
Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol. 2002;2:116–26.
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.
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.
Tsushima F, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T cell anergy. Blood. 2007;110:180–5.
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.
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.
Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.
Matthias S. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocr Relat Cancer. 2006;13:779–95.
Mary F, Barbara J. Dendritic cells: immune regulators in health and disease. Physiol Rev. 2002;82:97–130.
Zhou LJ, Thomas F. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. PNAS. 1996;93:2588–92.
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.
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.
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.
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.
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.
Sergey V, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008;112:1822–31.
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.
Acknowledgments
We would like to thank Haidong Xu (Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA) for critical reading of the manuscript, Prof. Yongquan Xue (The first affiliated hospital of Soochow University, China) for his fluorescence microscope technique support, and Dr. Jinfang Shen (Soochow University, China) for pathological support. This work was supported by the ‘‘Key Project of National Natural Science Foundation of China’’ (30770947), “135 Projects focus on Talent Foundation of Health Department of Jiangsu Province (RC2007075)” and “Medical Development Foundation of Jiangsu Province (H200712)”.
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Mu, CY., Huang, JA., Chen, Y. et al. 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. Med Oncol 28, 682–688 (2011). https://doi.org/10.1007/s12032-010-9515-2
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DOI: https://doi.org/10.1007/s12032-010-9515-2