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01.12.2006 | Original Article

Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA

verfasst von: Stefan Holdenrieder, Petra Stieber, Andrea Peterfi, Dorothea Nagel, Alexander Steinle, Helmut Rainer Salih

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2006

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Abstract

Expression of ligands of the immunoreceptor NKG2D such as MICA and MICB has been proposed to play an important role in the immunosurveillance of tumors. Proteolytic shedding of NKG2D ligands from cancer cells therefore constitutes an immune escape mechanism impairing anti-tumor reactivity by NKG2D-bearing cytotoxic lymphocytes. Serum levels of sMICA have been shown to be of diagnostic significance in malignant diseases of various origins. Here, we investigated the potential of soluble MICB, the sister molecule of MICA, as a marker in cancer and its correlation with soluble MICA. Analysis of MICB in sera of 512 individuals revealed slightly higher MICB levels in patients with various malignancies (N = 296; 95th percentile 216 pg/ml; P = 0.069) than in healthy individuals (N = 62; 95th percentile 51 pg/ml). Patients with benign diseases (N = 154; 95th percentile 198 pg/ml) exhibited intermediate MICB levels. In cancer patients, elevated MICB levels correlated significantly with cancer stage and metastasis (P = 0.007 and 0.007, respectively). Between MICB and MICA levels, only a weak correlation was found (r = 0.24). Combination of both markers resulted only in a slightly higher diagnostic power in the high specificity range. The reduction of MICA and MICB surface expression on cells by shedding and the effects of sMICA and sMICB in serum on host lymphocyte NKG2D expression might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. While MICB levels are not suited for the diagnosis of cancer in early stages, they may provide additional information for the staging of cancer disease.

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 285:727–729PubMedCrossRef

Groh V, Rhinehart R, Randolph-Habecker J, Topp MS, Riddell SR, Spies T (2001) Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol 2:255–260PubMedCrossRef

Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190PubMedCrossRef

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 96:6879–6884PubMedCrossRef

Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, Steinle A (2003) Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102:1389–1396PubMedCrossRef

Diefenbach A, Jensen ER, Jamieson AM, Raulet DH (2001) Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 413:165–171PubMedCrossRef

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 98:11521–11526PubMedCrossRef

Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274PubMedCrossRef

Pende D, Rivera P, Marcenaro S, Chang CC, Biassoni R, Conte R, Kubin M, Cosman D, Ferrone S, Moretta L, Moretta A (2002) Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res 62:6178–6186PubMed

10.

Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA 100:4120–4125PubMedCrossRef

11.

Friese MA, Wischhusen J, Wick W, Weiler M, Eisele G, Steinle A, Weller M (2004) RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo. Cancer Res 64:7596–7603PubMedCrossRef

12.

Kriegeskorte AK, Gebhardt FE, Porcellini S, Schiemann M, Stemberger C, Franz TJ, Huster KM, Carayannopoulos LN, Yokoyama WM, Colonna M, Siccardi AG, Bauer S, Busch DH (2005) NKG2D-independent suppression of T cell proliferation by H60 and MICA. Proc Natl Acad Sci USA 102:11805–11810PubMedCrossRef

13.

Salih HR, Rammensee HG, Steinle A (2002) Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 169:4098–4102PubMed

14.

Groh V, Wu J, Yee C, Spies T (2002) Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419:734–738PubMedCrossRef

15.

Yokoyama WM (2002) Immunology: catch us if you can. Nature 419:679–680PubMedCrossRef

16.

Holdenrieder S, Stieber P, Peterfi A, Nagel D, Steinle AL, Salih HR (2006) Soluble MICA in malignant diseases. Int J Cancer 118:684–687PubMedCrossRef

17.

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 171:6891–6899PubMed

18.

Wu JD, Higgins 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 114:560–568PubMed

19.

Raffaghello L, Prigione I, Airoldi I, Camoriano M, Levreri I, Gambini C, Pende D, Steinle A, Ferrone S, Pistoia V (2004) Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia 6:558–568PubMedCrossRef

20.

Welte SA, Sinzger C, Lutz SZ, Singh-Jasuja H, Sampaio KL, Eknigk U, Rammensee HG, Steinle A (2003) Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein. Eur J Immunol 33:194–203PubMedCrossRef

21.

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 USA 93:12445–12450PubMedCrossRef

22.

Schalhorn A, Fuerst H, Stieber P (2001) Tumor markers in lung cancer. J Lab Med 25:353–361

23.

Stieber P, Hasholzner U, Bodenmuller H, Nagel D, Sunder-Plassmann L, Dienemann H, Meier W, Fateh-Moghadam A (1993) CYFRA 21-1. A new marker in lung cancer. Cancer 72:707–713PubMedCrossRef

24.

Stieber P, Molina R, Chan DW, Fritsche HA, Beyrau R, Bonfrer JM, Filella X, Gornet TG, Hoff T, Jager W, van Kamp GJ, Nagel D, Peisker K, Sokoll LJ, Troalen F, Untch M, Domke I (2003) Clinical evaluation of the Elecsys CA 15-3 test in breast cancer patients. Clin Lab 49:15–24PubMed

25.

Molina R, Filella X, Auge JM (2004) ProGRP: a new biomarker for small cell lung cancer. Clin Biochem 37:505–511PubMedCrossRef

26.

Stieber P, Yamaguchi K (2002) ProGRP enables diagnosis of small-cell lung cancer. In: Diamandis EP, Frische HA, Lilja H, Chan DW, Schwartz MK (eds) Tumor markers; physiology, pathobiology, technology, and clinical applications, 1st edn. AACC, Washington, pp. 517–521

27.

Molina R, Filella X, Auge JM, Fuentes R, Bover I, Rifa J, Moreno V, Canals E, Vinolas N, Marquez A, Barreiro E, Borras J, Viladiu P (2003) Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors. Tumour Biol 24:209–218PubMedCrossRef

28.

Onda H, Ohkubo S, Shintani Y, Ogi K, Kikuchi K, Tanaka H, Yamamoto K, Tsuji I, Ishibashi Y, Yamada T, Kitada C, Suzuki N, Sawada H, Nishimura O, Fujino M (2001) A novel secreted tumor antigen with a glycosylphosphatidylinositol-anchored structure ubiquitously expressed in human cancers. Biochem Biophys Res Commun 285:235–243PubMedCrossRef

Titel: Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA
verfasst von: Stefan Holdenrieder
Petra Stieber
Andrea Peterfi
Dorothea Nagel
Alexander Steinle
Helmut Rainer Salih
Publikationsdatum: 01.12.2006
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 12/2006
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-006-0167-1

Springer Medizin

Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA

Abstract

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Springer Medizin

Abstract

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