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B7-H Abnormalities in Melanoma and Clinical Relevance

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Molecular Diagnostics for Melanoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1102))

Abstract

Melanoma have been shown to escape immune surveillance by different mechanisms such as loss of HLA class I antigens, upregulation of nonclassical HLA-G antigen and Fas, increased secretion of immune suppressive cytokines and metabolites as well as altered expression of co-stimulatory and coinhibitory signals. Recently, an important role of B7-H1 and B7-H4 in the immune escape of melanoma has been described. High mRNA and/or protein expression levels of these coinhibitory molecules were detected in both melanoma cell lines and melanoma lesions when compared to melanocytes. However, their clinical relevance is currently controversially discussed regarding a correlation of B7-H family members with tumor grading and staging as well as survival of patients in melanoma.

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Abbreviations

APC:

Antigen presenting cell

BTLA:

B- and T-lymphocyte attenuator

CTL:

Cytotoxic T lymphocyte

CTLA4:

Cytotoxic T-lymphocyte antigen 4

HLA:

Human leukocyte antigen

IFN:

Interferon

mAb:

Monoclonal antibody

MFI:

Mean specific fluorescence intensity

PBS:

Phosphate buffered saline

PD1:

Programmed cell death

TCR:

T cell receptor

TIL:

Tumor-infiltrating lymphocyte

β2-m:

β2-Microglobulin

References

  1. Harding FA et al (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356(6370):607–609

    Article  PubMed  CAS  Google Scholar 

  2. Sharpe AH, Freeman GJ (2002) The B7-CD28 superfamily. Nat Rev Immunol 2(2):116–126

    Article  PubMed  CAS  Google Scholar 

  3. Driessens G, Kline J, Gajewski TF (2009) Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev 229(1):126–144

    Article  PubMed  CAS  Google Scholar 

  4. Seliger B, Quandt D (2012) The expression, function, and clinical relevance of B7 family members in cancer. Cancer Immunol Immunother 61(8):1327–1341

    Article  PubMed  CAS  Google Scholar 

  5. Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477

    Article  PubMed  CAS  Google Scholar 

  6. Flies DB, Chen L (2007) The new B7s: playing a pivotal role in tumor immunity. J Immunother 30(3):251–260

    Article  PubMed  CAS  Google Scholar 

  7. Keir ME et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704

    Article  PubMed  CAS  Google Scholar 

  8. Postow MA, Harding J, Wolchok JD (2012) Targeting immune checkpoints: releasing the restraints on anti-tumor immunity for patients with melanoma. Cancer J 18(2):153–159

    Article  PubMed  CAS  Google Scholar 

  9. Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548

    Article  PubMed  Google Scholar 

  10. Seliger B et al (2008) The complex role of B7 molecules in tumor immunology. Trends Mol Med 14(12):550–559

    Article  PubMed  CAS  Google Scholar 

  11. Dong H et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800

    PubMed  CAS  Google Scholar 

  12. Yi KH, Chen L (2009) Fine tuning the immune response through B7-H3 and B7-H4. Immunol Rev 229(1):145–151

    Article  PubMed  CAS  Google Scholar 

  13. Chapoval AI et al (2001) B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol 2(3):269–274

    Article  PubMed  CAS  Google Scholar 

  14. Leitner J et al (2009) B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction. Eur J Immunol 39(7):1754–1764

    Article  PubMed  CAS  Google Scholar 

  15. Prasad DV et al (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity 18(6):863–873

    Article  PubMed  CAS  Google Scholar 

  16. Sica GL et al (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18(6):849–861

    Article  PubMed  CAS  Google Scholar 

  17. Zang X et al (2003) B7×: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A 100(18):10388–10392

    Article  PubMed  CAS  Google Scholar 

  18. Wilcox RA et al (2012) The B7 homologues and their receptors in hematologic malignancies. Eur J Haematol 88(6):465–475

    Article  PubMed  CAS  Google Scholar 

  19. Nishimura H, Honjo T (2001) PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 22(5):265–268

    Article  PubMed  CAS  Google Scholar 

  20. Arigami T et al (2011) Clinical significance of the B7-H4 coregulatory molecule as a novel prognostic marker in gastric cancer. World J Surg 35(9):2051–2057

    Article  PubMed  Google Scholar 

  21. Iwai Y et al (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 U S A 99(19):12293–12297

    Article  PubMed  CAS  Google Scholar 

  22. Blank C et al (2006) Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro. Int J Cancer 119(2):317–327

    Article  PubMed  CAS  Google Scholar 

  23. Gadiot J et al (2011) Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer 117(10):2192–2201

    Article  PubMed  CAS  Google Scholar 

  24. Kronig H et al (2012) PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. Int J Cancer 130(10):2327–2336

    Article  PubMed  Google Scholar 

  25. Quandt D et al (2011) B7-h4 expression in human melanoma: its association with patients’ survival and antitumor immune response. Clin Cancer Res 17(10):3100–3111

    Article  PubMed  CAS  Google Scholar 

  26. Hino R et al (2010) Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116(7):1757–1766

    Article  PubMed  Google Scholar 

  27. Martin-Orozco N et al (2010) Melanoma cells express ICOS ligand to promote the activation and expansion of T-regulatory cells. Cancer Res 70(23):9581–9590

    Article  PubMed  CAS  Google Scholar 

  28. He C et al (2011) The inhibitory role of b7-h4 in antitumor immunity: association with cancer progression and survival. Clin Dev Immunol 2011:695834

    Article  PubMed  Google Scholar 

  29. Zheng X et al (2012) Expression of costimulatory molecule B7-H4 in human malignant tumors. Onkologie 35(11):700–705

    Article  PubMed  CAS  Google Scholar 

  30. Mumprecht S et al (2009) Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood 114(8):1528–1536

    Article  PubMed  CAS  Google Scholar 

  31. Thompson RH et al (2005) Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer 104(10):2084–2091

    Article  PubMed  CAS  Google Scholar 

  32. Thompson RH et al (2004) Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 101(49):17174–17179

    Article  PubMed  CAS  Google Scholar 

  33. Curtin JA et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353(20):2135–2147

    Article  PubMed  CAS  Google Scholar 

  34. Tjin EP et al (2011) T-cell immune function in tumor, skin, and peripheral blood of advanced stage melanoma patients: implications for immunotherapy. Clin Cancer Res 17(17):5736–5747

    Article  PubMed  CAS  Google Scholar 

  35. Fourcade J et al (2010) Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 207(10):2175–2178

    Article  PubMed  CAS  Google Scholar 

  36. Taube JM et al (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4(127):127–137

    Article  Google Scholar 

  37. Strauss L et al (2008) Expression of ICOS on human melanoma-infiltrating CD4+CD25highFoxp3+ T regulatory cells: implications and impact on tumor-mediated immune suppression. J Immunol 180(5):2967–2980

    PubMed  CAS  Google Scholar 

  38. Viguier M et al (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173(2):1444–1453

    PubMed  CAS  Google Scholar 

  39. Fu T, HE Q, Sharma P (2011) The ICOS/ICOSL pathway is required for optimal antitumor responses mediated by anti-CTLA-4 therapy. Cancer Res 71(16):5445–5454

    Article  PubMed  CAS  Google Scholar 

  40. Zang X et al (2010) Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Mod Pathol 23(8):1104–1112

    Article  PubMed  CAS  Google Scholar 

  41. Fujimura T et al (2012) Regulatory T cells stimulate B7-H1 expression in myeloid-derived suppressor cells in ret melanomas. J Invest Dermatol 132(4):1239–1246

    Article  PubMed  CAS  Google Scholar 

  42. Blank C, Gajewski TF, Mackensen A (2005) 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 54(4):307–314

    Article  PubMed  CAS  Google Scholar 

  43. Fourcade J et al (2009) PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients. J Immunol 182(9):5240–5249

    Article  PubMed  CAS  Google Scholar 

  44. Brandt CS et al (2009) The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med 206(7):1495–1503

    Article  PubMed  CAS  Google Scholar 

  45. Li Y, Wang Q, Mariuzza RA (2011) Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6. J Exp Med 208(4):703–714

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported from grants of the Mildred Scheel Cancer Foundation, the Wilhelm Sander Foundation and the intramural Wilhelm Roux Program.

Author information

Authors and Affiliations

  1. Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany

    Barbara Seliger

Authors
  1. Barbara Seliger
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Editor information

Editors and Affiliations

  1. Cancer Diagnosis Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Magdalena Thurin

  2. Sidra Medical and Research Center,Qatar Foundation, Doha, Qatar

    Francesco M. Marincola

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Seliger, B. (2014). B7-H Abnormalities in Melanoma and Clinical Relevance. In: Thurin, M., Marincola, F. (eds) Molecular Diagnostics for Melanoma. Methods in Molecular Biology, vol 1102. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-727-3_19

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  • DOI: https://doi.org/10.1007/978-1-62703-727-3_19

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-726-6

  • Online ISBN: 978-1-62703-727-3

  • eBook Packages: Springer Protocols

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