Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2010

01-04-2010 | Original Article

Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer

Authors: Barbara Seliger, Robert Stoehr, Diana Handke, Anja Mueller, Soldano Ferrone, Bernd Wullich, Andrea Tannapfel, Ferdinand Hofstaedter, Arndt Hartmann

Published in: Cancer Immunology, Immunotherapy | Issue 4/2010

Login to get access

Abstract

Defects in HLA class I antigen processing machinery (APM) component expression often have a negative impact on the clinical course of tumors and on the response to T cell-based immunotherapy. Since only scant information is available about the frequency and clinical significance of HLA class I APM component abnormalities in prostate cancer, the APM component expression pattern was analyzed in 59 primary prostate carcinoma, adjacent normal tissues, as well as in prostate carcinoma cell lines. The IFN-γ inducible proteasome subunits LMP2 and LMP7, TAP1, TAP2, calnexin, calreticulin, ERp57, and tapasin are strongly expressed in the cytoplasm of normal prostate cells, whereas HLA class I heavy chain (HC) and β2-microglobulin are expressed on the cell surface. Most of the APM components were downregulated in a substantial number of prostate cancers. With the exception of HLA class I HC, TAP2 and ERp57 not detectable in about 0.5% of tumor lesions, all other APM components were not detected in at least 21% of lesions analyzed. These APM component defects were associated with a higher Gleason grade of tumors and an early disease recurrence. Prostate carcinoma cell lines also exhibit a heterogeneous, but reduced constitutive APM component expression pattern associated with lack or reduced HLA class I surface antigens, which could be upregulated by IFN-γ. Our results suggest that HLA class I APM component abnormalities are mainly due to regulatory mechanisms, play a role in the clinical course of prostate cancer and on the outcome of T cell-based immunotherapies.
Literature
1.
Epstein JI, Algabe F, Allsbrook WC, Bastacky S (2004) Tumours of the prostate. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA et al (eds) World Health Organization, classification of tumours. Pathology and genetic. Tumours of the urinary system and male genital organs. IARC, Lyon, pp 159–216
2.
Thompson TC (1990) Growth factors and oncogenes in prostate cancer. Cancer cells 2:345–354PubMed
3.
Risk M, Corman JM (2009) The role of immunotherapy in prostate cancer: an overview of current approaches in development. Rev Urol 11:16–27PubMed
4.
Chakraborty NG, Stevens RL, Mehrotra S, Laska E, Taxel P, Sporn JR, Schauer P, Albertsen PC (2003) Recognition of PSA-derived peptide antigens by T cells from prostate cancer patients without any prior stimulation. Cancer Immunol Immunother 52:497–505CrossRefPubMed
5.
Wang YS, Tsang YW, Chi CH, Cahng CC, Chu RM, Chi KH (2008) Synergistic anti-tumor effect of combination radio- and immunotherapy by electro-gene therapy plus intra-tumor injection of dendritic cells. Cancer Lett 266:275–285CrossRefPubMed
6.
Kiessling A, Füssel S, Wehner R, Bachmann M, Wirth MP, Rieber EP, Schmitz M (2008) Advances in specific immunotherapy for prostate cancer. Eur Urol 53:694–708PubMedCrossRef
7.
Olson WC, Heston WD, Rajasekaran AK (2007) Clinical trials of cancer therapies targeting prostate-specific membrane antigen. Rev Recent Clin Trials 2:182–190CrossRefPubMed
8.
Small EJ, Tchekmedyian NS, Rini BI, Fong L, Lowy I, Allison JP (2007) A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res 13:1810–1815CrossRefPubMed
9.
Fong L, Kwek SS, O’Brien S, Kavanagh B, McNeel DG, Weinberg V, Lin AM, Rosenberg J, Ryan CJ, Rini BI, Small EJ (2009) Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res 69:609–615CrossRefPubMed
10.
Theoret MR, Arlen PM, Pazdur M, Dahut WL, Schlom J, Gulley JL (2007) Phase I trail of an enhanced prostate-specific antigen-based vaccine and anti-CTLA-4 antibody in patients with metastatic androgen-independent prostate cancer. Clin Genitourin Cancer 5:347–350CrossRefPubMed
11.
Slovin SF (2008) Pitfalls or promise in prostate cancer immunotherapy which is winning? Cancer J 14:26–34CrossRefPubMed
12.
Burch PA, Breen JK, Buckner JC, Gastineau DA, Kaur JA, Laus RL, Padley DJ, Peshwa MV, Pitot HC, Richardson RL, Smits BJ, Sopapan P, Strang G, Valone FH, Vuk-Pavlović S (2000) Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res 6:2175–2182PubMed
13.
Eder JP, Kantoff PW, Roper K, Xu GX, Bubley GJ, Boyden J, Gritz L, Mazzara G, Oh WK, Arlen P, Tsang KY, Panicali D, Schlom J, Kufe DW (2000) A phase I trial of a recombinant vaccina virus expressing prostate-specific antigen in advanced prostate cancer. Clin Cancer Res 6:1632–1638PubMed
14.
Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M, Weber CE, Baccala AA, Goemann MA, Clift SM, Ando DG, Levitsky HI, Cohen LK, Sanda MG, Mulligan RC, Partin AW, Carter HB, Piantadosi S, Marshall FF, Nelson WG (2001) Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cell engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 59:5160–5168
15.
Hammer GE, Kanaseki T, Shastri N (2007) The final touches make perfect the peptide-MHC class I repertoire. Immunity 26:397–406CrossRefPubMed
16.
17.
Aptsiauri N, Cabrera T, Mendez R, Garcia-Lora A, Ruiz-Cabello F, Garrido F (2007) Role of altered expression of HLA class I molecules in cancer progression. Adv Exp Med Biol 601:123–131PubMed
18.
Cabrera T, Maleno I, Collado A, Lopez Nevot MA, Tait BD, Garrido F (2007) Analysis of HLA class I alterations in tumors: choosing a strategy based on known patterns of underlying molecular mechanisms. Tissue Antigens 1:264–268CrossRef
19.
Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S (2000) Escape of human solid tumor from T cell recognition: molecular mechanisms and functional significance. Adv Immunol 74:181–273CrossRefPubMed
20.
Seliger B, Ritz U, Ferrone S (2006) Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer 118:129–138CrossRefPubMed
21.
Sanda MG, Restifo NP, Walsh JC, Kawakami Y, Nelson WG, Pardoll DM, Simons JW (1995) Molecular characterization of defective antigen processing in human prostate cancer. J Natl Cancer Inst 87:280–285CrossRefPubMed
22.
Lee HM, Timme TL, Thompson TC (2000) Resistance to lysis by cytotoxic T cells: a dominant effect in metastatic mouse prostate cancer cells. Cancer Res 60:1927–1933PubMed
23.
Sharpe JC, Abel PD, Gilbertson JA, Brawn P, Foster CS (1994) Modulated expression of human leukocyte antigen class I and class II determinants in hyperplastic and malignant human prostatic epithelium. Br J Urol 74:609–616CrossRefPubMed
24.
Setiadi AF, David MD, Chen SS, Hiscott J, Jefferies WA (2005) Identification of mechanisms underlying transporter associated with antigen processing deficiency in metastatic murine carcinomas. Cancer Res 65:7485–7492CrossRefPubMed
25.
Kitamura H, Torigoe T, Asanuma H, Honma I, Sato N, Tsukamoto T (2007) Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition. J Urol 178:692–696CrossRefPubMed
26.
Stolzenburg JU, Rabenalt R, Do M, Kallidonis P, Liatsikos EN (2008) Endoscopic extraperitoneal radical prostatectomy: the University of Leipzig experience of 2000 cases. J Endourol 22:2319–2325CrossRefPubMed
27.
Sobin LH, Wittekind C (1997) TNM classification of malignant tumours. Wiley-Liss, New York, pp 172–175
28.
Kasper G, Weiser AA, Rump A, Sparbier K, Dahl E, Hartmann A, Wild P, Schwidetzky U, Castaños-Vélez E, Lehmann K (2005) Expression levels of putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients. Int J Cancer 117:961–973CrossRefPubMed
29.
van Oers JM, Wild PJ, Burger M, Denzinger S, Stoehr R, Rosskopf E, Hofstaedter F, Steyerberg EW, Klinkhammer-Schalke M, Zwarthoff EC, van der Kwast TH, Hartmann A (2007) FGFR3 mutations and normal CK20 staining pattern define low-grade noninvasive urothelial bladder tumors. Eur Urol 52:760–768CrossRefPubMed
30.
Stam NJ, Spits H, Ploegh HL (1986) Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 137:2299–2306PubMed
31.
Perosa F, Luccarelli G, Prete M, Favoino E, Ferrone S, Dammacco F (2003) Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide. J Immunol 171:1918–1926PubMed
32.
Lampson LA, Fisher CA, Whelan JP (1983) Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines. J Immunol 30:2471–2478
33.
Bandoh N, Ogino T, Cho HS, Hur SY, Shen J, Wang X, Kato S, Miyokawa N, Harabuchi Y, Ferrone S (2005) Development and characterization of human constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies. Tissue Antigens 66:185–194CrossRefPubMed
34.
Wang X, Campoli M, Cho HS, Ogino T, Bandoh N, Shen J, Hur SY, Kageshita T, Ferrone S (2005) A method to generate antigen-specific mAb capable of staining formalin-fixed, paraffin-embedded tissue sections. J. Immunol. Methods 299:139–151CrossRefPubMed
35.
Ogino T, Wang X, Kato S, Miyokawa N, Harabuchi Y, Ferrone S (2003) Endoplasmic reticulum chaperone-specific monoclonal antibodies for flow cytometry and immunohistochemical staining. Tissue Antigens 62:382–393CrossRef
36.
Temponi M, Kageshita T, Perosa F, Ono R, Okada H, Ferrone S (1989) Purification of murine IgG monoclonal antibodies by precipitation with caprylic acid: comparison with other methods of purification. Hybridoma 8:85–95CrossRefPubMed
37.
Norell H, Carlsten M, Ohlum T, Malmberg KJ, Masucci G, Schedvins K, Altermann W, Handke D, Atkins D, Seliger B, Kiessling R (2006) Frequent loss of HLA-A2 expression in metastasizing ovarian carcinomas associated with genomic haplotype loss and HLA-A2-restricted HER-2/neu-specific immunity. Cancer Res 66:6387–6394CrossRefPubMed
38.
Atkins D, Ferrone S, Schmahl GE, Störkel S, Seliger B (2004) Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma? J Urol 171:885–889CrossRefPubMed
39.
Armes JE, Trute L, White D, Southey MC, Hammet F, Tesoriero A, Hutchins AM, Dite GS, McCredie MR, Giles GG, Hopper JL, Venter DJ (1999) Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based-study. Cancer Res 59:2011–2017PubMed
40.
Seliger B, Atkins D, Bock M, Ritz U, Ferrone S, Huber C, Störkel S (2003) 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 95:1721–1727
41.
Blandes RA, Keating PJ, McWilliams LJ, George NJR, Stern PL (1995) Loss of HLA class I expression in prostate cancer: implications for immunotherapy. Urology 46:681–687CrossRef
42.
Bander NH, Yao D, Liu H, Chen YT, Steiner M, Zuccaro W, Moy P (1997) MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma. Prostate 33:233–239CrossRefPubMed
43.
Zhang H, Melamed J, Wei P, Cox K, Frankel W, Bahnson RR, Robinson N, Pyka R, Liu Y, Zheng P (2003) Concordant down-regulation of proto-oncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer. Cancer Immun 3:2PubMed
44.
Chang CC, Ogino T, Mullins DW, Oliver JL, Yamshchikov GV, Bandoh N, Slingluff CL Jr, Ferrone S (2006) Defective human leukocyte antigen class I-associated antigen presentation caused by a novel beta2-microglobulin loss-of-function in melanoma cells. J Biol Chem 281:18763–18773CrossRefPubMed
45.
Momburg F, Koch S (1989) Selective loss of beta 2-microglobulin mRNA in human colon carcinoma. J Exp Med 169:309–314CrossRefPubMed
46.
Vermeulen CF, Jordanova ES, ter Haar NT, Kolkman-Uljee SM, de Miranda NF, Ferrone S, Peters AA, Fleuren GJ (2007) Expression and genetic analysis of transporter associated with antigen processing in cervical carcinoma. Gynecol Oncol 105:593–599CrossRefPubMed
47.
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
48.
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 65:7926–7933PubMed
49.
Meissner M, Reichert TE, Kunkel M, Gooding W, Whiteside TL, Ferrone S, Seliger B (2005) Defects in the human leucocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clinical Cancer Res 11:2552–2560CrossRef
50.
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 57:197–206CrossRefPubMed
51.
Wright KL, White LC, Kelly A, Beck S, Trowsdale J, Ting JP (1995) Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. J Exp Med 181:1459–1471CrossRefPubMed
52.
Leys CM, Nomura S, LaFleur BJ, Ferrone S, Kaminishi M, Montgomery E, Goldenring JR (2007) Expression and prognostic significance of prothymosin-alpha and ERp57 in human gastric cancer. Surgery 141:41–50CrossRefPubMed
53.
Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Métivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed
54.
Panaretakis T, Joza N, Modjtahedi N, Tesniere A, Vitale I, Durchschlag M, Fimia GM, Kepp O, Piacentini M, Froehlich KU, van Endert P, Zitvogel L, Madeo F, Kroemer G (2008) The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death. Cell Death Differ 15:1499–1509CrossRefPubMed
55.
Clarke C, Smyth MJ (2007) Calreticulin exposure increases cancer immunogenicity. Nat Biotechnol 25:192–193CrossRefPubMed
Metadata
Title
Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer
Authors
Barbara Seliger
Robert Stoehr
Diana Handke
Anja Mueller
Soldano Ferrone
Bernd Wullich
Andrea Tannapfel
Ferdinand Hofstaedter
Arndt Hartmann
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 4/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-009-0769-5

Other articles of this Issue 4/2010

Cancer Immunology, Immunotherapy 4/2010 Go to the issue

Original Article

FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release

Original Article

Increase in tumor size following intratumoral injection of immunostimulatory CpG-containing oligonucleotides in a rat glioma model

Erratum

Erratum to: A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo

Original Article

Type I interferons inhibit the generation of tumor-associated macrophages

Original Article

Direct discovery and validation of a peptide/MHC epitope expressed in primary human breast cancer cells using a TCRm monoclonal antibody with profound antitumor properties

Original Article

Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-α for metastatic renal cell cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits