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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2009

01-09-2009 | Focussed Research Review

HLA and melanoma: multiple alterations in HLA class I and II expression in human melanoma cell lines from ESTDAB cell bank

Authors: Rosa Mendez, Natalia Aptsiauri, Ana Del Campo, Isabel Maleno, Teresa Cabrera, Francisco Ruiz-Cabello, Federico Garrido, Angel Garcia-Lora

Published in: Cancer Immunology, Immunotherapy | Issue 9/2009

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Abstract

Altered HLA class I and class II cell surface expression has been reported in many types of malignancy and represents one of the major mechanism by which tumour cells escape from T lymphocytes. In this report, we review the results obtained from the study of constitutive and IFN-gamma-induced expression of HLA class I and II molecules in 91 human melanoma cell lines from the European Searchable Tumour Cell Line Database, and compare them with published data on HLA expression in other types of cancer. Various types of alterations in HLA class I cell surface expression were found in a high percentage (67%) of the studied cell lines. These alterations range from total to selective HLA class I loss and are associated with β2-microglobulin gene mutations, transcriptional downregulation of HLA class I genes and antigen processing machinery components, or with the loss of heterozygosity in chromosome 6. The most frequently observed phenotype is selective downregulation of HLA-B locus, reversible after treatment with IFN-gamma. The expression of constitutive- or IFN-gamma induced-surface expression of at least one HLA class II locus is positive in 71.5% of the analysed cell lines. Four different HLA class II expression phenotypes were defined, and a positive correlation between the expression of class I and II molecules is discussed. More detailed information on the HLA expression patterns and others immunological characteristics of these melanoma cell lines can be found on the following website http://​www.​ebi.​ac.​uk/​ipd/​estdab.
Literature
1.
Altomonte M, Fonsatti E, Visintin A, Maio M (2003) Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach? Oncogene 22:6564–6569PubMedCrossRef
2.
Anichini A, Mortarini R, Nonaka D, Molla A, Vegetti C, Montaldi E, Wang X, Ferrone S (2006) Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients. Cancer Res 66:6405–6411PubMedCrossRef
3.
Aptsiauri N, Carretero R, Garcia-Lora A, Real LM, Cabrera T, Garrido F (2008) Regressing and progressing metastatic lesions: resistance to immunotherapy is predetermined by irreversible HLA class I antigen alterations. Cancer Immunol Immunother 57:1727–1733PubMedCrossRef
4.
Benitez R, Godelaine D, Lopez-Nevot MA, Brasseur F, Jiménez P, Marchand M, Oliva MR, van Baren N, Cabrera T, Andry G, Landry C, Ruiz-Cabello F, Boon T, Garrido F (1998) Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides. Tissue Antigens 52:520–529PubMedCrossRef
5.
Brady MS, Lee F, Petrie H, Eckels DD, Lee JS (2000) CD4(+) T cells kill HLA-class-II-antigen-positive melanoma cells presenting peptide in vitro. Cancer Immunol Immunother 48:621–626PubMedCrossRef
6.
Cabrera T, Ruiz-Cabello F, Garrido F (1995) Biological implications of HLA-DR expression in tumours. Scand J Immunol 41:398–406PubMedCrossRef
7.
Cabrera T, Angustias Fernandez M, Sierra A, Garrido A, Herruzo A, Escobedo A, Fabra A, Garrido F (1996) High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol 50:127–134PubMedCrossRef
8.
Cabrera T, Lara E, Romero JM, Maleno I, Real LM, Ruiz-Cabello F, Valero P, Camacho FM, Garrido F (2007) HLA class I expression in metastatic melanoma correlates with tumour development during autologous vaccination. Cancer Immunol Immunother 56:709–717PubMedCrossRef
9.
Dengjel J, Nastke MD, Gouttefangeas C, Gitsioudis G, Schoor O, Altenberend F, Müller M, Krämer B, Missiou A, Sauter M, Hennenlotter J, Wernet D, Stenzl A, Rammensee HG, Klingel K, Stevanović S (2006) Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas. Clin Cancer Res 12:4163–4170PubMedCrossRef
10.
Derré L, Corvaisier M, Charreau B, Moreau A, Godefroy E, Moreau-Aubry A, Jotereau F, Gervois N (2006) Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of cytotoxic effector cells. J Immunol 177:3100–3107PubMed
11.
Garcia-Lora A, Algarra I, Garrido F (2003) MHC class I antigens, immune surveillance, and tumour immune escape. J Cell Physiol 195:346–355PubMedCrossRef
12.
Garrido F, Cabrera T, Concha A, Glew S, Ruiz-Cabello F, Stern PL (1993) Natural history of HLA expression during tumour development. Immunol Today 14:491–499PubMedCrossRef
13.
Garrido F, Ruiz-Cabello F, Cabrera T, Pérez-Villar JJ, López-Botet M, Duggan-Keen M, Stern PL (1997) Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today 18:89–95PubMedCrossRef
14.
Garrido F, Cabrera T, Acolla RS, Bensa JC, Bodmer W, Dohr G, Drouet M, Fauchet R, Ferrara GB, Ferrone S, Giacomini P, Kageshita T, Koopman L, Maio M, Marincola F, Mazzilli C, Morel PA, Murray A, Papasteriades Crh, Salvaneschi L, Stern PL, Ziegler A (1997) HLA and cancer: 12th international histocompatibility workshop study. In: Charron D (ed) HLA, genetic diversity of HLA. Functional and medical implications, vol 1. EDK, p 445
15.
Garrido F, Algarra I (2001) MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 83:117–158PubMedCrossRef
16.
Gastl G, Ebert T, Finstad CL, Sheinfeld J, Gomahr A, Aulitzky W, Bander NH (1996) Major histocompatibility complex class I and class II expression in renal cell carcinoma and modulation by interferon gamma. J Urol 155:361–367PubMedCrossRef
17.
Ibrahim EC, Allory Y, Commo F, Gattegno B, Callard P, Paul P (2003) Altered pattern of major histocompatibility complex expression in renal carcinoma: tumour-specific expression of the nonclassical human leukocyte antigen-G molecule is restricted to clear cell carcinoma while up-regulation of other major histocompatibility complex antigens is primarily distributed in all subtypes of renal carcinoma. Am J Pathol 162:501–508PubMed
18.
Kageshita T, Hirai S, Ono T, Hicklin DJ, Ferrone S (1999) Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Am J Pathol 154:745–754PubMed
19.
Kageshita T, Ishihara T, Campoli M, Ferrone S (2005) Selective monomorphic and polymorphic HLA class I antigenic determinant loss in surgically removed melanoma lesions. Tissue Antigens 65:419–428PubMedCrossRef
20.
21.
Kobayashi H, Nagato T, Sato K, Aoki N, Kimura S, Murakami M, Iizuka H, Azumi M, Kakizaki H, Tateno M, Celis E (2007) Recognition of prostate and melanoma tumour cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner. Cancer Res 67:5498–5504PubMedCrossRef
22.
Koopman LA, Corver WE, van der Slik AR, Giphart MJ, Fleuren GJ (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191:961–976PubMedCrossRef
23.
Larrieu P, Ouisse LH, Guilloux Y, Jotereau F, Fonteneau JF (2007) A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumour cells to CD4+ T lymphocytes. Cancer Immunol Immunother 56:1565–1575PubMedCrossRef
24.
LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W (2004) Mini-review: specificity and expression of CIITA, the master regulator of MHC class II genes. Eur J Immunol 34:1513–1525PubMedCrossRef
25.
Li P, Gregg JL, Wang N, Zhou D, O’Donnell P, Blum JS, Crotzer VL (2005) Compartmentalization of class II antigen presentation: contribution of cytoplasmic and endosomal processing. Immunol Rev 207:206–217PubMedCrossRef
26.
Maccalli C, Li YF, El-Gamil M, Rosenberg SA, Robbins PF (2003) Identification of a colorectal tumour-associated antigen (COA-1) recognized by CD4(+) T lymphocytes. Cancer Res 63:6735–6743PubMed
27.
Mach B, Steimle V, Martinez-Soria E, Reith W (1996) Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14:301–331PubMedCrossRef
28.
Maleno I, López-Nevot MA, Cabrera T, Salinero J, Garrido F (2002) Multiple mechanisms generate HLA class I altered phenotypes in laryngeal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Cancer Immunol Immunother 51:389–396PubMedCrossRef
29.
Maleno I, Cabrera CM, Cabrera T, Paco L, López-Nevot MA, Collado A, Ferrón A, Garrido F (2004) Distribution of HLA class I altered phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Immunogenetics 56:244–253PubMedCrossRef
30.
Maleno I, Romero JM, Cabrera T, Paco L, Aptsiauri N, Cozar JM, Tallada M, López-Nevot MA, Garrido F (2006) LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas. Immunogenetics 58:503–510PubMedCrossRef
31.
Mandic M, Castelli F, Janjic B, Almunia C, Andrade P, Gillet D, Brusic V, Kirkwood JM, Maillere B, Zarour HM (2005) One NY-ESO-1-derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma. J Immunol 174:1751–1759PubMed
32.
Marín R, Ruiz-Cabello F, Pedrinaci S, Méndez R, Jiménez P, Geraghty DE, Garrido F (2003) Analysis of HLA-E expression in human tumours. Immunogenetics 54:767–775PubMed
33.
Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S (2000) Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 74:181–273PubMedCrossRef
34.
Matsushita K, Takenouchi T, Shimada H, Tomonaga T, Hayashi H, Shioya A, Komatsu A, Matsubara H, Ochiai T (2006) Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: possible involvement of c-myc suppression by interferon-gamma in situ. Cancer Sci 97:57–63PubMedCrossRef
35.
Mehta AM, Jordanova ES, Kenter GG, Ferrone S, Fleuren GJ (2008) Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother 57:197–206PubMedCrossRef
36.
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 11:2552–2560PubMedCrossRef
37.
Méndez R, Rodríguez T, Del Campo A, Monge E, Maleno I, Aptsiauri N, Jiménez P, Pedrinaci S, Pawelec G, Ruiz-Cabello F, Garrido F (2008) Characterization of HLA class I altered phenotypes in a panel of human melanoma cell lines. Cancer Immunol Immunother 57:719–729PubMedCrossRef
38.
Mizukami Y, Kono K, Maruyama T, Watanabe M, Kawaguchi Y, Kamimura K, Fujii H (2008) Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma. Br J Cancer 99:1462–1467PubMedCrossRef
39.
Nagorsen D, Scheibenbogen C, Marincola FM, Letsch A, Keilholz U (2003) Natural T cell immunity against cancer. Clin Cancer Res 9:4296–4303PubMed
40.
Novellino L, Castelli C, Parmiani G (2005) A listing of human tumour antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 54:187–207PubMedCrossRef
41.
Paschen A, Song M, Osen W, Nguyen XD, Mueller-Berghaus J, Fink D, Daniel N, Donzeau M, Nagel W, Kropshofer H, Schadendorf D (2005) Detection of spontaneous CD4+ T-cell responses in melanoma patients against a tyrosinase-related protein-2-derived epitope identified in HLA-DRB1*0301 transgenic mice. Clin Cancer Res 11:5241–5247PubMedCrossRef
42.
Pawelec G, Marsh S (2006) ESTDAB: a collection of immunologically characterised melanoma cell lines and searchable databank. Cancer Immunol Immunother 55:623–627PubMedCrossRef
43.
Ramal LM, Maleno I, Cabrera T, Collado A, Ferron A, Lopez-Nevot MA, Garrido F (2000) Molecular strategies to define HLA haplotype loss in microdissected tumour cells. Hum Immunol 61:1001–1012PubMedCrossRef
44.
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(4):512–518PubMedCrossRef
45.
Reith W, LeibundGut-Landmann S, Waldburger JM (2005) Regulation of MHC class II gene expression by the class II transactivator. Nat Rev Immunol 5:793–806PubMedCrossRef
46.
Rimsza LM, Roberts RA, Miller TP, Unger JM, LeBlanc M, Braziel RM, Weisenberger DD, Chan WC, Muller-Hermelink HK, Jaffe ES, Gascoyne RD, Campo E, Fuchs DA, Spier CM, Fisher RI, Delabie J, Rosenwald A, Staudt LM, Grogan TM (2004) Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumour immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood 103:4251–4258PubMedCrossRef
47.
Robbins PF, El-Gamil M, Li YF, Zeng G, Dudley M, Rosenberg SA (2002) Multiple HLA class II-restricted melanocyte differentiation antigens are recognized by tumour-infiltrating lymphocytes from a patient with melanoma. J Immunol 169:6036–6047PubMed
48.
Rodríguez T, Méndez R, Del Campo A, Jiménez P, Aptsiauri N, Garrido F, Ruiz-Cabello F (2007) Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines. BMC Cancer 7:34PubMedCrossRef
49.
Rodríguez T, Méndez R, Del Campo A, Aptsiauri N, Martín J, Orozco G, Pawelec G, Schadendorf D, Ruiz-Cabello F, Garrido F (2007) Patterns of constitutive and IFN-gamma inducible expression of HLA class II molecules in human melanoma cell lines. Immunogenetics 59:123–133PubMedCrossRef
50.
Röhn TA, Reitz A, Paschen A, Nguyen XD, Schadendorf D, Vogt AB, Kropshofer H (2005) A novel strategy for the discovery of MHC class II-restricted tumour antigens: identification of a melanotransferrin helper T-cell epitope. Cancer Res 65:10068–10078PubMedCrossRef
51.
Rolland P, Deen S, Scott I, Durrant L, Spendlove I (2007) Human leukocyte antigen class I antigen expression is an independent prognostic factor in ovarian cancer. Clin Cancer Res 13:3591–3596PubMedCrossRef
52.
Sabapathy K, Nam SY (2008) Defective MHC class I antigen surface expression promotes cellular survival through elevated ER stress and modulation of p53 function. Cell Death Differ 15:1364–1374PubMedCrossRef
53.
Speetjens FM, de Bruin EC, Morreau H, Zeestraten EC, Putter H, van Krieken JH, van Buren MM, van Velzen M, Dekker-Ensink NG, van de Velde CJ, Kuppen PJ (2008) Clinical impact of HLA class I expression in rectal cancer. Cancer Immunol Immunother 57:601–609PubMedCrossRef
54.
van den Elsen PJ, Gobin SJ, van Eggermond MC, Peijnenburg A (1998) Regulation of MHC class I and II gene transcription: differences and similarities. Immunogenetics 48:208–221PubMedCrossRef
55.
van Duinen SG, Ruiter DJ, Broecker EB, van der Velde EA, Sorg C, Welvaart K, Ferrone S (1988) Level of HLA antigens in locoregional metastases and clinical course of the disease in patients with melanoma. Cancer Res 48:1019–1025PubMed
56.
van Houdt IS, Sluijter BJ, Moesbergen LM, Vos WM, de Gruijl TD, Molenkamp BG, van den Eertwegh AJ, Hooijberg E, van Leeuwen PA, Meijer CJ, Oudejans JJ (2008) Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumour infiltrating T-lymphocytes and preserved MHC class I antigen expression. Int J Cancer 123:609–615PubMedCrossRef
57.
Watson NF, Ramage JM, Madjd Z, Spendlove I, Ellis IO, Scholefield JH, Durrant LG (2006) Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. Int J Cancer 118:6–10PubMedCrossRef
Metadata
Title
HLA and melanoma: multiple alterations in HLA class I and II expression in human melanoma cell lines from ESTDAB cell bank
Authors
Rosa Mendez
Natalia Aptsiauri
Ana Del Campo
Isabel Maleno
Teresa Cabrera
Francisco Ruiz-Cabello
Federico Garrido
Angel Garcia-Lora
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-009-0701-z

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