Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon-γ and -β

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  • 1 Departments of Neurosurgery and Biochemistry, University of Yamanashi Faculty of Medicine, Yamanashi, Japan
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Object

It remains unclear whether malignant glioma cells can deliver tumor antigens efficiently to major histocompatibility complex (MHC) Class I molecules. To elucidate the mechanism of antigen presentation in malignant gliomas, the authors examined the expression of the transporter associated with antigen processing 1 (TAP1), which transports antigens to MHC Class I molecules, and low-molecular-mass polypeptide 2 (LMP2), which is a subunit of a proteasome. They also analyzed the effects of interferon (IFN)-γ and IFN-β on the expression of these molecules.

Methods

Five glioma cells expressed undetectable or very low levels of TAP1 protein and did not express TAP1 messenger (m)RNA. Normal brain tissue and glioma tissue specimens also showed undetectable levels of TAP1 protein and the same levels of LMP2 protein as lymphoblastoid B cells. Treatments of the tumor cells with IFN-γ or -β enhanced the expression of both TAP1 protein and mRNA as well as the expression of MHC Class I molecules. The expression of LMP2 protein was not altered by the IFN treatments. The authors analyzed structural alterations in the TAP1 promoter region in eight malignant glioma cell lines. Single nucleotide polymorphism was found in 446 bp upstream of the translation start site of the TAP1 gene, and a point mutation was found in 34 bp upstream of the TAP1 gene.

Conclusions

Malignant glioma cells may be less immunogenic due to low levels of TAP1 expression. Upregulated expression of TAP1 and MHC Class I molecules by IFN-γ and -β may enhance antigen presentation in malignant glioma cells.

Abbreviations used in this paper:

CTL = cytotoxic T lymphocyte; GAS = gamma activating sequence; GBM = glioblastoma multiforme; IFN = interferon; ISRE = IFN-stimulated response element; LMP = low-molecular-mass polypeptide; MHC = major histocompatibility complex; mRNA = messenger RNA; NF = nuclear factor; PBS = phosphate-buffered saline; PCR = polymerase chain reaction; SD = standard deviation; SNP = single nucleotide polymorphism; TAP = transporter associated with antigen processing..

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  • 1

    Beck S, , Kelly A, , Radley E, , Khurshid F, , Alderton RP, & Trowsdale J: DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing. J Mol Biol 228:433441, 1992

    • Search Google Scholar
    • Export Citation
  • 2

    Cromme FV, , Airey J, , Heemels MT, , Ploegh HL, , Keating PJ, & Stern PL, et al.: Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J Exp Med 179:335340, 1994

    • Search Google Scholar
    • Export Citation
  • 3

    Deverson EV, , Gow IR, , Coadwell WJ, , Monaco JJ, , Butcher GW, & Howard JC: MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature 348:738741, 1990

    • Search Google Scholar
    • Export Citation
  • 4

    Driscoll J, , Brown MG, , Finley D, & Monaco JJ: MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature 365:262264, 1993

    • Search Google Scholar
    • Export Citation
  • 5

    Gaczynska M, , Rock KL, & Goldberg AL: γ-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365:264267, 1993

    • Search Google Scholar
    • Export Citation
  • 6

    Glynne R, , Powis SH, , Beck S, , Kelly A, , Kerr LA, & Trowsdale J: A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature 353:357360, 1991

    • Search Google Scholar
    • Export Citation
  • 7

    Heimberger AB, , Crotty LE, , Archer GE, , McLendon RE, , Friedman A, & Dranoff G, et al.: Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma. J Neuroimmunol 103:1625, 2000

    • Search Google Scholar
    • Export Citation
  • 8

    Jamaluddin M, , Wang S, , Garofalo RP, , Elliott T, , Casola A, & Baron S, et al.: IFN-β mediates coordinate expression of antigen-processing genes in RSV-infected pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 280:L248L257, 2001

    • Search Google Scholar
    • Export Citation
  • 9

    Kageshita T, , Hirai S, , Ono T, , Hicklin DJ, & Ferrone S: Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Am J Pathol 154:745754, 1999

    • Search Google Scholar
    • Export Citation
  • 10

    Kaklamanis L, , Townsend A, , Doussis-Anagnostopoulou IA, , Mortensen N, , Harris AL, & Gatter KC: Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am J Pathol 145:505509, 1994

    • Search Google Scholar
    • Export Citation
  • 11

    Kamarashev J, , Ferrone S, , Seifert B, , Boni R, , Nestle FO, & Burg G, et al.: TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis. Int J Cancer 95:2328, 2001

    • Search Google Scholar
    • Export Citation
  • 12

    Kikuchi T, , Akasaki Y, , Irie M, , Homma S, , Abe T, & Ohno T: Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother 50:337344, 2001

    • Search Google Scholar
    • Export Citation
  • 13

    Kobayashi T, , Yamanaka R, , Homma J, , Tsuchiya N, , Yajima N, & Yoshida S, et al.: Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with malignant glioma. Cancer Immunol Immunother 52:632637, 2003

    • Search Google Scholar
    • Export Citation
  • 14

    Korkolopoulou P, , Kaklamanis L, , Pezzella F, , Harris AL, & Gatter KC: Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 73:148153, 1996

    • Search Google Scholar
    • Export Citation
  • 15

    Ma W, , Lehner PJ, , Cresswell P, , Pober JS, & Johnson DR: Interferon-γ rapidly increases peptide transporter (TAP) subunit expression and peptide transport capacity in endothelial cells. J Biol Chem 272:1658516590, 1997

    • Search Google Scholar
    • Export Citation
  • 16

    Matsui M, , Machida S, , Itani-Yohda T, & Akatsuka T: Downregulation of the proteasome subunits, transporter, and antigen presentation in hepatocellular carcinoma, and their restoration by interferon-γ. J Gastroenterol Hepatol 17:897907, 2002

    • Search Google Scholar
    • Export Citation
  • 17

    Min W, , Pober JS, & Johnson DR: Interferon induction of TAP1: the phosphatase SHP-1 regulates crossover between the IFN-α/β and the IFN-γ signal-transduction pathways. Circ Res 83:815823, 1998

    • Search Google Scholar
    • Export Citation
  • 18

    Nagy N, , Vanky F, & Klein E: Tumor surveillance: expression of the transporter associated with antigen processing (TAP-1) in ex-vivo human tumor samples and its elevation by in vitro treatment with IFN-α and TNF-γ. Immunol Lett 64:153160, 1998

    • Search Google Scholar
    • Export Citation
  • 19

    Neefjes JJ, , Momburg F, & Hammerling GJ: Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science 261:769771, 1993

    • Search Google Scholar
    • Export Citation
  • 20

    Ortiz-Navarrete V, , Seelig A, , Gernold M, , Frentzel S, , Kloetzel PM, & Hammerling GJ: Subunit of the ‘20S’ proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature 353:662664, 1991

    • Search Google Scholar
    • Export Citation
  • 21

    Parney IF, , Farr-Jones MA, , Chang LJ, & Petruk KC: Human glioma immunobiology in vitro: implications for immunogene therapy. Neurosurgery 46:11691178, 2000

    • Search Google Scholar
    • Export Citation
  • 22

    Powis SJ, , Townsend ARM, , Deverson EV, , Bastin J, , Butcher GW, & Howard JC: Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature 354:528531, 1991

    • Search Google Scholar
    • Export Citation
  • 23

    Restifo NP, , Esquivel F, , Kawakami Y, , Yewdell JW, , Mule JJ, & Rosenberg SA, et al.: Identification of human cancers deficient in antigen processing. J Exp Med 177:265272, 1993

    • Search Google Scholar
    • Export Citation
  • 24

    Seliger B, , Atkins D, , Bock M, , Ritz U, , Ferrone S, & Huber C, et al.: Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation. Clin Cancer Res 9:17211727, 2003

    • Search Google Scholar
    • Export Citation
  • 25

    Seliger B, , Bock M, , Ritz U, & Huber C: High frequency of a nonfunctional TAP1/LMP2 promoter polymorphism in human tumors. Int J Oncol 20:349353, 2002

    • Search Google Scholar
    • Export Citation
  • 26

    Seliger B, , Dunn T, , Schwenzer A, , Casper J, , Huber C, & Schmoll HJ: Analysis of the MHC class I antigen presentation machinery in human embryonal carcinomas: evidence for deficiencies in TAP, LMP and MHC class I expression and their upregulation by IFN-γ. Scand J Immunol 46:625632, 1997

    • Search Google Scholar
    • Export Citation
  • 27

    Seliger B, , Hammers S, , Höhne A, , Zeidler R, , Knuth A, & Gerharz C, et al.: IFN-γ-mediated coordinated transcriptional regulation of the human TAP-1 and LMP-2 genes in human renal cell carcinoma. Clin Cancer Res 3:573578, 1997

    • Search Google Scholar
    • Export Citation
  • 28

    Shi L, , Yan G, , Fu Y, , Ma L, , Penfornis A, & Faustman D: Human TAP1 polymorphisms detected by denaturing gradient gel electrophoresis. Tissue Antigens 49:421426, 1997

    • Search Google Scholar
    • Export Citation
  • 29

    Spies T, , Cerundolo V, , Colonna M, , Cresswell P, , Townsend A, & Demars R: Presentation of viral antigen by MHC class I molecules is dependent on a putative peptide transporter heterodimer. Nature 355:644646, 1992

    • Search Google Scholar
    • Export Citation
  • 30

    Spies T, & Demars R: Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature 351:323324, 1991

    • Search Google Scholar
    • Export Citation
  • 31

    Townsend ARM, , Gotch FM, & Davey J: Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell 42:457467, 1985

  • 32

    Townsend ARM, , Rothbard J, , Gotch FM, , Bahadur G, , Wraith D, & McMichael AJ: The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959968, 1986

    • Search Google Scholar
    • Export Citation
  • 33

    Trowsdale J, , Hanson I, , Mockridge I, , Beck S, , Townsend A, & Kelly A: Sequences encoded in the class II region of the MHC related to the ‘ABC’ superfamily of transporters. Nature 348:741744, 1990

    • Search Google Scholar
    • Export Citation
  • 34

    Van Kaer L, , Ashton-Rickardt PG, , Ploegh HL, & Tonegawa S: TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell 71:12051214, 1992

    • Search Google Scholar
    • Export Citation
  • 35

    Vitale M, , Rezzani R, , Rodella L, , Zauli G, , Grigolato P, & Caudei M, et al.: HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res 58:737742, 1998

    • Search Google Scholar
    • Export Citation
  • 36

    Wright KL, , White LC, , Kelly A, , Beck S, , Trowsdale J, & Ting JPY, et al.: Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. J Exp Med 181:14591471, 1995

    • Search Google Scholar
    • Export Citation
  • 37

    Yu JS, , Wheeler CJ, , Zeltzer PM, , Ying H, , Finger DN, & Lee PK, et al.: Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 61:842847, 2001

    • Search Google Scholar
    • Export Citation
  • 38

    Yung WK, , Castellanos AM, , Van Tassel P, , Moser RP, & Marcus SG: A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma. J Neurooncol 9:2934, 1990

    • Search Google Scholar
    • Export Citation
  • 39

    Zhang L, , Yamane T, , Satoh E, , Amagasaki K, , Kawataki T, & Asahara T, et al.: Establishment and patial characterization of five malignant glioma cell lines. Neuropathology 25:136143, 2005

    • Search Google Scholar
    • Export Citation

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