Journal of Cancer Research and Clinical Oncology

, Volume 134, Issue 9, pp 1021–1027 | Cite as

B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression

  • Lei Geng
  • Dongsheng Huang
  • Junwei Liu
  • Yigang Qian
  • Junfang Deng
  • Donglin Li
  • Zhenhua Hu
  • Jian Zhang
  • Guoping Jiang
  • Shusen ZhengEmail author
Original Paper



Aberrant tumor cell B7-H1 expression, a member of B7 family that can predominantly stimulate interleukin 10 (IL-10) products, contributed to the tumor immune evasion and tumor progression. This study was designed to investigate the expression of B7-H1 and IL-10 in normal pancreas tissues and pancreatic carcinoma samples, and to evaluate clinical significance of B7-H1 expression in pancreatic carcinoma.


First, the B7-H1 and IL-10 expression in 40 pancreatic carcinoma samples and 8 healthy pancreas specimens using reverse transcription-PCR (RT-PCR) and western-blotting was detected. Localization of B7-H1 and IL-10 was confirmed by immunohistochemical (IHC) staining. Next, the association between B7-H1 expression and tumor differentiation and tumor stage was analyzed. Finally, the correlation between tumor-associated B7-H1 and IL-10 was evaluated.


Pancreatic carcinoma samples demonstrated the up-regulated expression of B7-H1 and IL-10 at mRNA and protein level compared with normal pancreas tissues. IHC staining revealed that B7-H1 and IL-10 was almost localized in tumor cells. Analysis of relationship between B7-H1 and tumor clinicopathological characteristics showed that B7-H1 expression was significantly associated with poor tumor differentiation (P < 0.01) and advanced tumor stage (P < 0.01). Meanwhile, tumor-associated B7-H1 expression was also correlated with IL-10 products (P < 0.01, R 2 = 0.6985, mRNA level; P < 0.01, R 2 = 0.7236, protein level) in tumor cells.


Our findings for the first time demonstrated up-regulated B7-H1 expression in human pancreatic carcinoma tissues, which might play a role in tumor progression and invasiveness. This expression seemed to be related to the ability of B7-H1 to promoting IL-10 secretion.


B7-H1 Pancreatic carcinoma Interleukin-10 



Bovine serum albumin






Myeloid dendritic cells


Programmed death 1


Reverse transcription-PCR


Tumor node metastasis



This work was supported by grants from the National Key Basic Research Program of China (No.2003CB515501) and Science and Technology Department of Zhejiang Province (No. 2006C33027).


  1. Akdis CA, Blaser K (2001) Mechanisms of interleukin-10-mediated immune suppression. Immunology 103:131–148PubMedCrossRefGoogle Scholar
  2. Bellone G., Turletti A, Artusio E, Mareschi K, Carbone A, Tibaudi D, Robecchi A, Emanuelli G., Rodeck U (1999) Tumor-associated transforming growth factor-ß and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am J Pathol 155:537–547PubMedGoogle Scholar
  3. Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, Collins M, Honjo T, Freeman GJ, Carreno BM (2002) PD-1: PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol 32:634–643PubMedCrossRefGoogle Scholar
  4. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567PubMedCrossRefGoogle Scholar
  5. Dong H, Zhu G., Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5:1365–1369PubMedCrossRefGoogle Scholar
  6. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800PubMedGoogle Scholar
  7. Erdman SE, Rao VP, Poutahidis T, Ihrig MM, Ge Z, Feng Y, Tomczak M, Rogers AB, Horwitz BH, Fox JG (2003) CD4+CD25+ regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63:6042–6050PubMedGoogle Scholar
  8. Geng L, Jiang G, Fang Y, Dong S, Xie H, Chen Y, Shen M, Zheng S (2006) B7-H1 expression is up-regulated in peripheral blood CD14+ monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levels. J Viral Hepat 13:725–733PubMedCrossRefGoogle Scholar
  9. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99:12293–12297PubMedCrossRefGoogle Scholar
  10. Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA, Koulmanda M, Freeman GJ, Sayegh MH, Sharpe AH (2006) Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med 203:883–895PubMedCrossRefGoogle Scholar
  11. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimur M (2004) 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 10:5094–5100PubMedCrossRefGoogle Scholar
  12. Moore KW, de Waal Malefyt R, Coffman RL, O’ Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol l19:683–765CrossRefGoogle Scholar
  13. Sarkar FH, Banerjee S, Li Y (2006) Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol 11 [Epub ahead of print]Google Scholar
  14. Strome SE, Dong H, Tamura H, Voss SG., Flies DB, Tamada K, Salomao D, Cheville J, Hirano F, Lin W, Kasperbauer JL, Ballman KV, Chen L (2003) B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res 63:6501–6505PubMedGoogle Scholar
  15. Tamura H, Dong H, Zhu G., Sica GL, Flies DB, Tamada K, Chen L (2001) B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood 97:1809–1816PubMedCrossRefGoogle Scholar
  16. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Krejci KG, Lobo JR, Sengupta S, Chen L, Zincke H, Blute ML, Strome SE, Leibovich BC, Kwon ED (2004) Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci USA 101:17174–17179PubMedCrossRefGoogle Scholar
  17. Trabattoni D, Saresella M, Biasin M, Boasso A, Piacentini L, Ferrante P, Dong H, Maserati R, Shearer GM, Chen L, Clerici M (2003) B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression. Blood 101:2514–2520PubMedCrossRefGoogle Scholar
  18. Vicari AP, Trinchieri G (2004) Interleukin-10 in viral disease and cancer: exiting the labyrinth? Immunol Rev 202:223–236PubMedCrossRefGoogle Scholar
  19. Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, Weller M, Wiendl H (2003) Expression of the b7-related molecule b7-h1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 63:7462–7467PubMedGoogle Scholar
  20. Zou W (2005) Immunosuppresive networks in the tumor environment and their therapeutic relevance. Nat Rev Cancer 5:262–274CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Lei Geng
    • 1
  • Dongsheng Huang
    • 2
  • Junwei Liu
    • 2
  • Yigang Qian
    • 1
  • Junfang Deng
    • 1
  • Donglin Li
    • 1
  • Zhenhua Hu
    • 1
  • Jian Zhang
    • 3
  • Guoping Jiang
    • 1
  • Shusen Zheng
    • 1
    Email author
  1. 1.Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Department of Hepato-Biliary-Pancreatic SurgeryFirst Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
  2. 2.Department of General SurgerySir Run Run Shaw Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
  3. 3.Department of AnesthesiologyFirst Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina

Personalised recommendations