HLA Class I Antigen Abnormalities in Tumors

  • Barbara Seliger
  • Soldano Ferrone


Major Histocompatibility Complex Class Uveal Melanoma Antigen Processing Machinery Antigen Processing Machinery Component Transporter Associate With Antigen Presentation Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ostrand-Rosenberg S (2004) Animal models of tumor immunity, immunotherapy and cancer vaccines. Curr. Opin. Immunol. 16:143–150PubMedCrossRefGoogle Scholar
  2. 2.
    Rosenberg SA, Yang JC, Retifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10:909–915PubMedCrossRefGoogle Scholar
  3. 3.
    Braud V, Jones E Y, McMichel A (1997) The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9. Eur. J. Immunol. 27:1164–1169PubMedCrossRefGoogle Scholar
  4. 4.
    Ulbrecht M, Modrow R, Srivastava R, Pedersen P, Weiss EH (1998) Interaction of HLA-E with peptides and the peptide transporter in vitro: implications for its function in antigen presentation. J. Immunol. 160:4375–4385PubMedGoogle Scholar
  5. 5.
    Ishitani A, Geraghty DE (1992) Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc. Natl. Acad. Sci. USA 89:3947–3951PubMedCrossRefGoogle Scholar
  6. 6.
    O’ Callaghan CA, Bell JI (1998) Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. Immunol. Rev. 163:129–38CrossRefGoogle Scholar
  7. 7.
    Paul P, Cabestre FA, Ibrahim EC, Lefebvre S, Hhalil-Daher I, Vazeux G, Quiles RM, Bermond F, Dausset J, Carosella ED (2000) Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and –G7 transcripts in human transfected cells. Hum. Immunol. 61:1138–1149PubMedCrossRefGoogle Scholar
  8. 8.
    Kumanovics A, Takada T, Lindahl KF (2003) Genomic organization of the mammalian MHC. Annu. Rev. Immunol. 21:629PubMedCrossRefGoogle Scholar
  9. 9.
    Bahram S, Spies T (1996) Nucleotide sequence of a human MHC class I MICB cDNA. Immunogenet. 43:230–233Google Scholar
  10. 10.
    Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729PubMedCrossRefGoogle Scholar
  11. 11.
    Bahram S (2000) MIC genes: from genetics to biology. Adv. Immunol. 76:1–60PubMedGoogle Scholar
  12. 12.
    Natali PG, Bigotti A, Nicotra MR, Viora M, Manfredi D, Ferrone S (1984) Distribution of human class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin. Cancer Res. 44:4679–4687PubMedGoogle Scholar
  13. 13.
    Rousseau P, Masternak K, Krawczyk M, Reith W, Dausset J, Carosella ED, Moreau P (2004) In vivo, RFX5 binds differently to the human leukocyte antigen-E, -F, and -G gene promoters and participates in HLA class I protein expression in a cell type-dependent manner. Immunol. 111:53–65CrossRefGoogle Scholar
  14. 14.
    Crisa L, McMaster MT, Ishii JK, Fischer SJ, Salomon DR. (1997) Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts. J. Exp. Med. 186:289–298PubMedCrossRefGoogle Scholar
  15. 15.
    Loke YW, King A, Burrows T, Gardner L, Bowen M, Hiby S, Howlett S, Holmes N, Jacobs D (1997) Evaluation of trophoblast HLA-G antigen with a specific monoclonal antibody. Tissue Antigens 50:135–146PubMedCrossRefGoogle Scholar
  16. 16.
    Le Discorde M, Moreau P, Sabatier P, Legeais JJ, Carosella ED (2003) Expression of HLA-G in human cornea, an immune-privileged tissue. Hum. Immunol. 64:1039–1044PubMedCrossRefGoogle Scholar
  17. 17.
    Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T (1999) Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc. Natl. Acad. Sci. USA 96:6879–6884PubMedCrossRefGoogle Scholar
  18. 18.
    Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T (1996) Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc. Natl. Acad. Sci. U S A. 93:12445–12450PubMedCrossRefGoogle Scholar
  19. 19.
    Chiang EY, Stroynowski I (2004) A non-classical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor. J. Immunol. 173:4394–4401PubMedGoogle Scholar
  20. 20.
    Braud V, Allan DSJ, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI. Phillips JH et al. (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B, and C. Nature 391:795–799PubMedCrossRefGoogle Scholar
  21. 21.
    Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, Geraghty DE (1998) HLA-E is the major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc. Natl. Acad. Sci. USA 95:5199–5204PubMedCrossRefGoogle Scholar
  22. 22.
    Khalil-Daher I, Riteau B, Menier C, Sedlik C, Paul P, Dausset J, Carosella ED, Rouas-Freiss N (1999) Role of HLA-G versus HLA-E on NK function: HLA-G is able to inhibit NK cytolysis by itself. J. Reprod. Immunol. 43:175–182PubMedCrossRefGoogle Scholar
  23. 23.
    Hofmeister V, Weiss EH (2003) HLA-G modulates immune responses by diverse receptor interactions. Semin. Cancer Biol. 13:317–323PubMedCrossRefGoogle Scholar
  24. 24.
    Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial gamma-delta T cells. Science 279:1737–1740PubMedCrossRefGoogle Scholar
  25. 25.
    Groh V, Rhinehart R, Randolph-Habecker J, Topp MS, Riddell SR, Spies T (2001) Costimulation of CD8 alph/abeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat. Immunol. 2:255–260PubMedCrossRefGoogle Scholar
  26. 26.
    Cerwenka A, Lanier LL (2003) NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer, Tissue Antigens 61:335–343Google Scholar
  27. 27.
    Raulet DH (2003) Roles of the NKG2D immunoreceptor and its ligands. Nat. Rev. Immunol. 3:781–790PubMedCrossRefGoogle Scholar
  28. 28.
    Bahram S, Inoko H, Shiina T, Radosavljevic M (2005) MIC and other NKG2D ligands: from none to too many. Curr. Opin. Immunol.17:505–509PubMedGoogle Scholar
  29. 29.
    Trombetta ES, Mellman I (2005) Cell biology of antigen processing in vitro and in vivo. Ann. Rev. Immunol. 23:975–1028CrossRefGoogle Scholar
  30. 30.
    Ackerman A L, Kyritsis C, Tampé R and Cresswell P (2003) Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens. Proc. Natl. Acad. Si. USA 100:12889–12894CrossRefGoogle Scholar
  31. 31.
    Rivett AJ, Hearn AR (2004) Proteasome function in antigen presentation: immunoproteasome complexes, peptide production, and interactions with viral proteins. Curr. Protein Pept. Sci. 5:153–161PubMedCrossRefGoogle Scholar
  32. 32.
    Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, van Endert PM (2002) Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat. Immunol. 6:689–697CrossRefGoogle Scholar
  33. 33.
    Serwold T, Gonzalez F, Kim J, Jacob R, Shastri N (2002) ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 419:480–483PubMedCrossRefGoogle Scholar
  34. 34.
    Paulsson K, Wang P (2003) Chaperones and folding of MHC class I molecules in the endoplasmic reticulum. Biochim. Biophys. Acta. 1641:1–12PubMedCrossRefGoogle Scholar
  35. 35.
    Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, Lopez-Botet M, Duggan-Keen M, Stern PL (1997) Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol. Today 18:89–95PubMedCrossRefGoogle Scholar
  36. 36.
    Garcia-Lora A, Martinez M, Algarra I, Gaforio JJ, Garrido F (2003) MHC class I-deficient metastatic tumor variants immunoselected by T lymphocytes originate from the coordinated downregulation of APM components. Int. J. Cancer 106:521–527PubMedCrossRefGoogle Scholar
  37. 37.
    Murray PG, Constandinou CM, Crocker J, Young LS, Ambinder RF (1998) Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin’s disease. Blood 92:2477–83PubMedGoogle Scholar
  38. 38.
    Wetzler M, Baer MR, Stewart SJ, Donohue K, Ford L, Stewart CC, Repasky EA, Ferrone S (2001) HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse. Leukemia 15:128–133PubMedCrossRefGoogle Scholar
  39. 39.
    Demant C, Mulder A, Deneys V, Worsham MJ, Maes P, Claas FH, Ferrone S (2004) Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack? Blood. 103:3122–30Google Scholar
  40. 40.
    Lehmann F, Marchand M, Hainaut P, Pouillart P, Sastre X, Ikeda H, Boon T, Coulie PG. (1995) Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. Eur. J. Immunol. 25:340–347PubMedCrossRefGoogle Scholar
  41. 41.
    Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, Rosenberg SA. (1996) Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst. 88:100–108PubMedCrossRefGoogle Scholar
  42. 42.
    Kloor M, Becker C, Benner A, Woerner SM, Gebert J, Ferrone S, von Knebel Doeberitz M (2005) Immunoselective pressure and human leukocyte antigen class I antigen machinery defects in microsatellite unstable colorectal cancers. Cancer Research 65:6418–6424PubMedCrossRefGoogle Scholar
  43. 43.
    Algarra I, Garcia-Lora A. Cabrera T, Ruiz-Cabello F and Garrido F (2004) The selection of tumor variants with altered expression of classical and non-classical MHC class I molecules: implications for tumor immune escape. Cancer Immunol. Immunother. 53:904–910PubMedCrossRefGoogle Scholar
  44. 44.
    Seliger B, Maeurer MJ, Ferrone S (2000) Antigen-processing machinery breakdown and tumor growth. Immunol. Today. 21:455–64PubMedCrossRefGoogle Scholar
  45. 45.
    Chang CC, Campoli M, Pestifo NP, Wang X, Ferrone S (2005) Immune selection of hot-spot UPbeta2-microglobulin gene mutations, HLA-A2 allospecificity loss, and antigen-processing machinery component down-regulation in melanoma cells derived from recurrent metastases following immunotherapy. J. Immunol. 174:1462–1474PubMedGoogle Scholar
  46. 46.
    Bicknell DC, Kaklamanis L, Hampson R, Bodmer WF, Karran P (1996) Selection for ss2-microglobulin mutation in mismatch repair defective colorectal carcinomas. Curr. Biol. 6:1695–1697PubMedCrossRefGoogle Scholar
  47. 47.
    Cabrera CM, Jimenez P, Cabrera T, Esparza C, Ruiz-Cabello F, Garrido F (2003) Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways: b2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors. Tissue Antigens 61:211–219PubMedCrossRefGoogle Scholar
  48. 48.
    Chen HL, Gabrilovich D, Tampe R, Girgis KR, Nadaf S, Carbone DP (1996) A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nat. Genet.13:210–213PubMedCrossRefGoogle Scholar
  49. 49.
    Benitez R, Godelaine D, Lopez-Nevot MA et al. (1998) Mutations of the ss2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides. Tissue Antigens 52:520–529PubMedGoogle Scholar
  50. 50.
    Hicklin DJ, Wang Z, Arienti F, Rivoltini L, Parmiani G, Ferrone S (1998) beta2-microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma. J. Clin. Invest. 101:break2720–2729Google Scholar
  51. 51.
    Feenstra M, rozemuller E, Duran K, Stuy I, van den Tweel J, Slootweg P, de Weger R, Tilanus M. (1999) Mutation in the beta 2m gene is not a frequent event in head and neck squamous cell carcinomas. Hum Immunol. 60:697–706PubMedCrossRefGoogle Scholar
  52. 52.
    Atkins D, Ferrone S, Schmahl GE, Storkel S, Seliger B (2004) Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma. J. Urol. 171:885–889PubMedCrossRefGoogle Scholar
  53. 53.
    Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V (2005) Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene 24:4634–4644PubMedCrossRefGoogle Scholar
  54. 54.
    Romero JM, Jiménez P, Cabrera T, Cózar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F (2005) Coordinated downregulation of the antigen presentation machinery and HLA class I/?2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer. Int. J. Cancer 113:605–610PubMedCrossRefGoogle Scholar
  55. 55.
    Cabrera CM, Jimenez P, Concha A, Garrido F, Ruiz-Cabello F (2004) Promyelocytic leukemia (PML) nuclear bodies are disorganized in colorectal tumors with total loss of major histocompatibility complex class I expression and LMP7 downregulation. Tissue Antigens 63:446–452PubMedCrossRefGoogle Scholar
  56. 56.
    Seliger B, Ritz U, Abele R, Bock M, Tampe R, Sutter G, Drexler I, Huber C, Ferrone S (2001) Immune escape of melanoma: First evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway. Cancer Res. 61:8647–8650PubMedGoogle Scholar
  57. 57.
    Vitale M, Pelusi G, Taroni B, Gobbi G, Micheloni C, Rezzani R, Donato F, Wang X, Ferrone S (2005) HLA class I antigen down-regulation in primari ovary carcinoma lesions: association with disease stage. Clin. Cancer Res. 11:67–72PubMedGoogle Scholar
  58. 58.
    Fowler NL, Frazer IH (2004) Mutations in TAP genes are common in cervical carcinomas. Gynecol. Oncol. 92:914–921PubMedCrossRefGoogle Scholar
  59. 59.
    Yang T, McNally BA, Ferrone S, Liu Y, Zheng P (2003) A single-nucleotide deletion leads to rapid degradation of TAP-1 mRNA in a melanoma cell line. J. Biol. Chem. 278:15291–15296PubMedCrossRefGoogle Scholar
  60. 60.
    Dutta N, Majumder D, Gupta A, Mazumber DN, Banerjee S (2005) Analysis of human lymphocyte antigen class I expression in gastric cancer by reverse transcriptase-polymerase chain reaction. Hum. Immunol. 66 :164–169PubMedCrossRefGoogle Scholar
  61. 61.
    Sheu BC, Chiou SH, Chang WC, Chow SN, Lin HH, Chen RJ, Huang SC, Ho HN, Hsu SM (2005) Integration of high risk human papillomavirus DNA correlates with HLA genotype aberration and reduced HLA class I molecule expression in human cervical carcinoma. Clin. Immunol. 115:295–301PubMedCrossRefGoogle Scholar
  62. 62.
    Ashrafi GH, Haghshenas MR, Marchetti B, O’Brien PM, Campo MS (2005) E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I. Int. J. Cancer 113:276–283PubMedCrossRefGoogle Scholar
  63. 63.
    Seliger B, Dunn T, Schwenzer A, Casper J, Huber C, Schmoll HJ (1997) Analysis of the MHC class I kantigen presentation machinery in human embryonal carcinomas: evidence for deficiencies in TAP, LMP and MHC class I expression and their upregulation by IFN-gamma. Scand J Immunol. 46:625–32PubMedCrossRefGoogle Scholar
  64. 64.
    Marrogi AJ, Munshi A, Merogi AJ, Ohadike Y, El-Habashi A, Marrogi OL, Freeman SM (1997) Study of tumor infiltrating lymphocytes and transforming growth factor-ss as prognostic factors in breast carcinoma. Int. J. Cancer 74:492–501PubMedCrossRefGoogle Scholar
  65. 65.
    Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 58:3491–3494PubMedGoogle Scholar
  66. 66.
    Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H. (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res. 61:5132–5136PubMedGoogle Scholar
  67. 67.
    Schumacher K, Haensch W, Roefzaad C, Schlag PM (2001) Prognostic significance of activated CD8+ T cell infiltrations within esophageal carcinomas. Cancer Res. 61:3932–3936PubMedGoogle Scholar
  68. 68.
    Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med. 348:203–213PubMedCrossRefGoogle Scholar
  69. 69.
    Prall F, Dührkop T, Weirich V et al (2004) Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability. Hum. Pathol. 35:808–816PubMedCrossRefGoogle Scholar
  70. 70.
    Al-Batran SE, Rafiyan MR, Atmaca A, Neumann A, Karbach J, Bender A, Weidmann E, Altmannsberger HM, Knuth A and Jager E (2005) Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma. Cancer Res. 65:3937–3941PubMedCrossRefGoogle Scholar
  71. 71.
    Sandel MH, Speetjens FM, Menon AG, Albertsson PA, Basse PH, Hokland M, Nagelkerke JF, Tollenaar RA EM, van de Velde CJH, Kuppen PJK (2005) Natural killer cells infiltrating colorectal cancer and MHC class I expression. Mol. Immunol. 42:541–546PubMedCrossRefGoogle Scholar
  72. 72.
    Menon AG, Fleuren GJ, Alphenaar EA, Jonges LE., Janssen van Rhijn CM, Ensink NG, Putter H, Tollenaar RA, van de Velde CJ, Kuppen PJ (2002a) A basal membrane-like structure surrounding tumor nodules may prevent intraepithelial leukocyte infiltration in colorectal cancer. Cancer Immunol. Immunother. 52:121–126Google Scholar
  73. 73.
    Scrivener S, Goddard R, Kaminski E, Prentice A (2003) Abnormal T-cell function in B-cell chronic lymphocytic leukaemia. Leuk. Lymphoma 44:383–389PubMedCrossRefGoogle Scholar
  74. 74.
    Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Hadaf S, Kavanaugh D, Carbone DP (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med. 2:1096–1103PubMedCrossRefGoogle Scholar
  75. 75.
    Medema JP, de Jong J, van Hall T, Melief CJ, Offringa R (1999) Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J. Exp. Med. 190:1033–1038PubMedCrossRefGoogle Scholar
  76. 76.
    Coleman S, Clayton A, Mason MD, Jasani B, Adams M, Tabi Z (2005) Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer. Cancer Res. 65:7000–7006PubMedCrossRefGoogle Scholar
  77. 77.
    Liotta LA, Kohn EC (2001) The microenvironment of the tumor-host interface. Nature 411:375–379PubMedCrossRefGoogle Scholar
  78. 78.
    Gilboa E (2004) The promise of cancer vaccines. Nat. Rev. Cancer 4:401–411PubMedCrossRefGoogle Scholar
  79. 79.
    Kammertoens T, Schüler T, Blankenstein T (2005) Immunotherapy: target the stroma to hit the tumor, Trends Mol Med.11:225–31Google Scholar
  80. 80.
    Spiotto MT, Schreiber H. (2005) Rapid destruction of the tumor microenvironment by CTLs recognizing cancer-specific antigens cross-presented by stromal cells. Cancer Immunity 5:8.PubMedGoogle Scholar
  81. 81.
    Qin Z, Blankenstein T (2004) A cancer immunosurveillance controversy. Nat. Immunol. 5:3–4PubMedCrossRefGoogle Scholar
  82. 82.
    Willimsky G., Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–6PubMedCrossRefGoogle Scholar
  83. 83.
    Campoli M, Ferrone S, Zea AH, Rodriguez PC, Ochoa AC (2005) Mechanisms of tumor evasion. Cancer Treat. Res. 123:61–88PubMedCrossRefGoogle Scholar
  84. 84.
    Cromme FV, Airey J, Heemels MT et al. (1994) Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J. Exp. Med. 179:335–340PubMedCrossRefGoogle Scholar
  85. 85.
    Kaklamanis L, Townsend A, Doussis-Anagnostopoulou IA, Mortensen N, Harris AL, Gatter KC (1994) Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am. J. Pathol. 145:505–509PubMedGoogle Scholar
  86. 86.
    Kaklamanis L, Leek R, Koukourakis M, Gatte KC, Harris AL (1995) Loss of transporter in antigen processing 1 transport protein and major histocompatibility complex class I molecules in metastatic versus primary breast cancer. Cancer Res. 55:5191–5194PubMedGoogle Scholar
  87. 87.
    Vitale M, Rezzani R, Rodella L, Zauli G, Grigolato P, Cadei M, Hicklin DJ, Ferrone S (1998) HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res. 58:737–742PubMedGoogle Scholar
  88. 88.
    Le YS, Kim TE, Kim BK et al (2002) Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers. Exp. Mol. Med. 34:18–26PubMedGoogle Scholar
  89. 89.
    Krishnakumar S, Lakshmi SA, Abhyankar D, Biswa J (2004) Transporter associated protein expression in uveal melanoma. Br. J. Ophthalmol. 88:925–928PubMedCrossRefGoogle Scholar
  90. 90.
    Meissner M, Reichert TE, Kunkel M, Gooding W, Whiteside TL, Ferrone S, Seliger B (2005) Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin. Cancer Res. 11:2552–2560PubMedCrossRefGoogle Scholar
  91. 91.
    Kallfelz M, Jung D, Hilmes C, Knuth A, Jaeger E, Huber C, Seliger B (1999) Induction of immunogenicity of a human renal-cell carcinoma cell line by TAP1-gen transfer. Int. J. Cancer.81: 125–133Google Scholar
  92. 92.
    Qin Z, Harders C, Cao X, Huber C, Blankenstein T, Seliger B (2002) Increased tumorigenicity, but unchanged immunogenicity, of transporter for antigen presentation 1-deficient tumors. Cancer Res. 62:2856–2860PubMedGoogle Scholar
  93. 93.
    Lou Y, Vitalis TZ, Basha G, Cai B, Chen SS, Choi KB, Jeffries AP, Elliott WM, Atkins D, Seliger B, Jefferies WA (2005) Restoration of the expression of transporters associated with antigen processing in lung carcinoma increases tumor-specific immune responses and survival. Cancer Res. 65:7926–7933PubMedGoogle Scholar
  94. 94.
    Parmiani G, Castelli C, Dalerba P, Mortarini R, Rivoltini L, Marincola FM, Anichini A (2002) Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going. J. Natl. Cancer Inst. 94:805–818PubMedGoogle Scholar
  95. 95.
    Agrawal S, Reemtsma K, Bagiella E, Oluwole SF and Braunstein NS (2004) Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma. Cell. Immunol. 228:130–137PubMedCrossRefGoogle Scholar
  96. 96.
    Jager MJ, Hurks HM, Levitskaya J, Kiessling R (2002) HLA expression in uveal melanoma: there is no rule without some exception. Hum. Immunol. 63:444–451PubMedCrossRefGoogle Scholar
  97. 97.
    Menon AG, Morreau H, Tollenaar RA, Alphenaar E, Van Puijenbroek M, Putter H, Janssen-Van Rhijn CM, Van De Velde CJ, Fleuren GJ, Kuppen PJ (2002b) Down-regulation of HLA-A expression correlates with a better prognosis in colorectal cancer patients. Lab. Invest. 82:1725–1733Google Scholar
  98. 98.
    Madjd Z, Spendlove I, Pinder SE, Ellis IO, Durrant LG (2005) Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int. J. Cancer 117:248–255PubMedCrossRefGoogle Scholar
  99. 99.
    Ramnath N, Tan D, Li Q, Hylander BL, Bogner P, Ryes L, Ferrone S (2005) Is downregulation of MHC class I antigen expression in human non-small cell lung carcinoma associated with prolonged survival? Cancer Immunol. Immunother. 27:1–9Google Scholar
  100. 100.
    Cao B, Tian X, Li Y, Jiang P, Ning T, Xing H, Zhao Y, Zhang C, Shi X, Chen D, Shen Y, Ke Y (2005) LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. Carcinogen. 26:1280–1284CrossRefGoogle Scholar
  101. 101.
    Seliger B, Bock M, Ritz U, Huber C (2002) High frequency of a non-functional TAP1/LMP2 promoter polymorphism in human tumors. Int. J. Oncol. 20:349–353 sPubMedGoogle Scholar
  102. 102.
    McCluskey J, Rossjohn J, Purcell AW (2004) TAP genes and immunity. Curr. Opin. Immunol. 16:651–659PubMedCrossRefGoogle Scholar
  103. 103.
    Ibrahim EC, Aractingi S, Allory Y, Borrini F, Dupuy A, Duvillard P, Carosella ED, Avril MF, Paul P (2004) Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype. Int. J. Cancer 108:243–250CrossRefPubMedGoogle Scholar
  104. 104.
    Real LM, Cabrera T, Collado A, Jimenez P, Garcia A, Ruiz-Cabello F, Garrido F (1999) Expression of HLA-G in human tumors is not a frequent event. Int. J. Cancer 81:512–518PubMedCrossRefGoogle Scholar
  105. 105.
    Fukushima Y, Oshika Y, Nakamura M, Tokunaga T, Hatanaka H, Abe Y, Yamazaki H, Kijima H, Ueyama Y, Tamaoki N (1998) Increased expression of human histocompatibility leucocyte antigen-G in colorectal cancer cells. Int. J. Mol. Med. 2:349–351PubMedGoogle Scholar
  106. 106.
    Paul P, Rouas-Freiss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal FA, Avril MF, Dausset J, Guillet JG, Carosella ED (1998) HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proc. Natl. Acad. Sci. USA 95:4510–4515PubMedCrossRefGoogle Scholar
  107. 107.
    Paul P, Canestre FA, Le Gal FA, Khalil-Daher I, Le Danff C, Schmid M, Mercier S, Avril MF, Dausset J, Guillet JG, Carosella ED (1999) Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer Res. 59:1954–1960PubMedGoogle Scholar
  108. 108.
    Ibrahim EC, Morange M, Dausset J, Carosella ED, Paul P (2000) Heat shock and arsenite induce expression of the non-classical class I histocompatibility HLA-G gene in tumor cell lines. Cell Stress Chaperones 5:207–218PubMedCrossRefGoogle Scholar
  109. 109.
    Ibrahim EC, Guerra N, Lacombe MJ, Angevin E, Chouaib S, Carosella ED, Caignard A, Paul P (2001) Tumor up-regulaton of the non-classical class I HLA-G antigen expression in renal carcinoma. Cancer Res. 61: 6838–6845Google Scholar
  110. 110.
    Urosevic M, Kurrer MO, Kamarashev J, Mueller B, Weder W, Burg G, Stahel RA, Dummer R, Trojan A (2001) Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology human leukocyte antigen class I loss and interleukin-10 production. Am. J. Pathol. 159:817–824PubMedGoogle Scholar
  111. 111.
    Wiendl H, Mitsdoerffer M, Hofmeister V, Wischhusen J, Bornemann A, Meyermann R, Weis EH, Melms A, Weller M (2002) A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J. Immunol. 168:4772–4780PubMedGoogle Scholar
  112. 112.
    Chang CC, Ferrone S (2003) HLA-G in melanoma: can the current controversies be solved? Semin. Cancer Biol. 13:361–369CrossRefGoogle Scholar
  113. 113.
    Davidson B, Elstrand MB, McMaster MT, Berner A, Kurman RJ., Risberg B, Trope CG. Shih IM (2005) HLA-G expression in effusions is a possible marker of tumor susceptibility to chemotherapy in ovarian carcinoma. Gynecol. Oncol. 96:42–47PubMedCrossRefGoogle Scholar
  114. 114.
    Urosevic M, Willers J, Mueller B, Kempf W, Burg G, Dummer R (2002a) HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas. Blood 99:609–617CrossRefGoogle Scholar
  115. 115.
    Urosevic M, Kempf W, Zagrodnik B, Panizzon R, Burg G, Dummer R (2005) HLA-G expression in basal cell carcinomas of the skin recurring after radiotherapy. Clin. Exp. Dermatol. 30:422–425PubMedCrossRefGoogle Scholar
  116. 116.
    Marin R, Ruiz-Cabello F, Pedrinaci S, Mendez R, Jimenez P, Geraghty DE, Garrido F (2003) Analysis of HLA-E expression in human tumors. Immunogenet. 54:767–775Google Scholar
  117. 117.
    Palmisano GL, Contardi E, Morabito A, Gargaglione V, Ferrara GB, Pistillo MP (2005) HLA-E surface expression is independent of the availability of HLA class I signal sequence-derived peptides in human tumor cell lines. Hum. Immunol. 66:1–12PubMedCrossRefGoogle Scholar
  118. 118.
    Mouillot G, Marcou C, Rousseau P, Rouas-Freiss N, Carosella ED, Moreau P (2005) HLA-G gene activation in tumor cells involves cis-acting epigenetic changes, Int. J. Cancer 113:928–936CrossRefGoogle Scholar
  119. 119.
    Rouas-Freiss N, Bruel S, Menier C, Marcou C, Moreau P, Carosella ED (2005) Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis. Int. J. Cancer 117:114–122PubMedCrossRefGoogle Scholar
  120. 120.
    Urosevic M, Trojan A, Dummer R (2002b) HLA-G and its KIR ligands in cancer-another enigma yet to be solved? J. Pathol. 196:252–253CrossRefGoogle Scholar
  121. 121.
    Wagner SN, Rebmann V, Willers CP, Grosse-Wilde H, Goos M (2000) Expression analysis of classic and non classical HLA molecules before interferon alfa-2b treatment of melanoma. Lancet 356:220–221PubMedCrossRefGoogle Scholar
  122. 122.
    Ugurel S, Rebmann V, Ferrone S, Tilgen W, Grosse-Wilde H, Reinhold U (2001) Soluble human leukocyte antigen-G serum level is elevated in melanoma patient and is further increased by interferon-alpha immunotherapy. Cancer 92:369–376PubMedCrossRefGoogle Scholar
  123. 123.
    Lefebvre S, Antioin, Uzan S, McMaster M, Dausset J, Carosella ED, Paul P (2002) Specific activation of the non-classical class I histocompatibility HLA-G antigen and expression of the ILT2 inhibitory receptor in human breast cancer. J. Pathol. 196:266–274PubMedCrossRefGoogle Scholar
  124. 124.
    Rebmann V, Regel J, Stolke D, Grosse-Wilde H. (2003) Secretion of sHLA-G molecules in malignancies. Semin Cancer Biol. 13:371–7PubMedCrossRefGoogle Scholar
  125. 125.
    Tomasec P, Braud VM, Rickards C, Powell MB, McSharry BP, Gadola S, Cerundolo V, Borysiewicz LK, McMichael AJ, Wilkinson GW (2000) Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40. Science 287:1031Google Scholar
  126. 126.
    Ljunggren HG, Karre K (1985) Host resistance directed selectively against H-2-deficient lymphoma variants: analysis of the mechanism. J. Exp. Med. 162:1745–1759PubMedCrossRefGoogle Scholar
  127. 127.
    Vetter CS, Groh V, thor Straten P, Spies T, Brocker EB, Becker JC (2002) Expression of stress- induced MHC class I related chain molecules on human melanoma. J. Invest. Dermatol. 118:600–605PubMedCrossRefGoogle Scholar
  128. 128.
    Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, Kimura R, Miyagi T, Mochizuki K, Sasaki Y, Hayashi N (2003) Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Int. J. Cancer. 104:354–361PubMedCrossRefGoogle Scholar
  129. 129.
    Salih HR, Rammensee HG, Steinle A (2002) Down-regulation of MICA on human tumors by proteolytic shedding. J. Immunol. 169:4098–4102PubMedGoogle Scholar
  130. 130.
    Groh V, Wu J, Yee C, Spies T (2002) Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419:734–738PubMedCrossRefGoogle Scholar
  131. 131.
    Vetter CS, Lieb W, Bröcker EB, Becker JC (2004) Loss of nonclassical MHC molecules MIC-A/B expression during progression of uveal melanoma. Brit. J. Cancer 91:1495–1499PubMedGoogle Scholar
  132. 132.
    Wu JD, Higgin LM, Steinle A, Cosman D, Haugk K, Plymate SR (2004) Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J. Clin. Invest. 114:560–568PubMedCrossRefGoogle Scholar
  133. 133.
    Watson NF, Spendlove I, Madjg Z, McGilvray R, Green AR, Ellis IO, Scholefield JH, Durrant LG (2005) Expression of the stress-related MHC class I chain-related protein MICA is an indicator of good prognosis in colorectal cancer patients. Int. J. Cancer 118:1445–52CrossRefGoogle Scholar
  134. 134.
    Cerwenka A, Baron JL, Lanier LL (2001) Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc. Natl. Acad. Sci. USA 98:11521–11526PubMedCrossRefGoogle Scholar
  135. 135.
    Germain C, Larbouret C, Cesson V, Donda A, Held W, Mach JP, Pelegrin A, Robert B (2005) MHC class I-related chain A conjugated to antitumor antibodies can sensitize tumor cells to specific lysis by natural killer cells. Clin. Cancer Res. 11:7516–7522PubMedCrossRefGoogle Scholar
  136. 136.
    Doubrovina ES, Doubrovin MM, Vider E, Sisson RB, O’Reilly RJ, Dupont B, Vyas YM (2003) Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J. Immunol. 171:6891–6899PubMedGoogle Scholar
  137. 137.
    Wiemann K, Mittrucker HW, Feger U, Welte SA, Yokoyama WM, Spies T, Rammensee HG, Steinle A (2005) Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo. J. Immunol. 175:720–729PubMedGoogle Scholar
  138. 138.
    Rivoltini L, Canese P, Huber V, Iero M, Pilla L, Valenti R, Fais S, Lozupone F, Casati C, Castelli C, Parmiani G (2005) Escape strategies and reasons for failure in the interaction between tumor cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opin. Biol. Ther. 5:463–476Google Scholar
  139. 139.
    Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD, Schreiber H (1999) CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. USA 96:8633–8638PubMedCrossRefGoogle Scholar
  140. 140.
    Qin Z, Schwartzkopff J, Pradera F, Kammertoens T, Seliger B, Pircher H, Blankenstein T (2003) A critical requirement of interferon gamma-mediated angiostasis for tumor rejection by CD8+ T cells. Cancer Res. 63:4095–4100PubMedGoogle Scholar
  141. 141.
    Chen HL, Gabrilovich D, Virmani A, Ratnani I, Girgis KR, Nadaf-Rahrof S, Fernandez-Vina M, Carbone DP. (1996) Structural and functional analysis of beta2 microglobulin abnormalities in human lung and breast cancer. Int J Cancer. 67:756–63PubMedCrossRefGoogle Scholar
  142. 142.
    Krishnakumar S, Sundaram A, Abhyankar D, Krishnamurthy V, Shanmugam MP, Gopal L, Sharma T, Biswas J (2004) Major histocompatibility antigens and antigen-processing molecules in retinoblastoma. Cancer 100:1059–1069PubMedCrossRefGoogle Scholar
  143. 143.
    Lee N, Geraghty DE (2003) HLA-F surface expression on B cell and monocyte cell lines is partially independent from tapasin and completely independent from TAP. J. Immunol. 171:5264–5271PubMedGoogle Scholar
  144. 144.
    York IA, Grant EP, Dahl AM, Rock KL (2005) A mutant cell with a novel defect in MHC class I quality control. J. Immunol. 174:6839–6846PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Barbara Seliger
    • 1
  • Soldano Ferrone
    • 1
  1. 1.Institute of Medical Immunology, Martin Luther University, 06112 HalleGermany and Department of Immunology, Roswell Park Cancer InstituteBuffaloUSA

Personalised recommendations