Abstract
Tumor produces a number of immunosuppressive factors that block maturation of dendritic cells (DCs). Here, we demonstrated that endogenous factors presented in the serum of patients with prostate cancer (CaP) inhibited the generation of functionally active DCs from CD14+ monocytes in vitro. We have shown a significant inhibitory potential of serum obtained from patients with CaP and benign prostate hyperplasia benign prostatic hyperplasia (BPH) when compared with serum from healthy volunteers. As assessed by flow cytometry, expression of CD83, CD86, and CD40 molecules was strongly inhibited by CaP and BPH serum. In addition, these DCs were weak stimulators of allogeneic T cell proliferation when compared with DCs produced in the presence of healthy volunteer serum. Statistical analysis of the results revealed a positive relationship between the inhibition of expression of DC markers CD83 and CD80 and the levels of serum-free prostate-specific antigen (PSA). These data suggest that the DC system may be impaired in CaP patients.
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References
Aalamian, M., Pirtskhalaishvili, G., Nunez, A., Esche, C., Shurin, G.V., Huland, E., Huland, H. and Shurin, M.R. (2001) Human prostate cancer regulates generation and maturation of monocyte-derived dendritic cells. Prostate 46, 68–75.
Aalamian, M., Tourkova, I.L., Chatta, G.S., Lilja, H., Huland, E., Huland, H., Shurin, G.V. and Shurin, M.R. (2003) Inhibition of dendropoiesis by tumor derived and purified prostate specific antigen. J. Urol. 170, 2026–2030.
Armstrong, T.D., Pulaski, B.A. and Ostrand-Rosenberg, S. (1998) Tumor antigen presentation: changing the rules. Cancer Immunol. Immunother. 46, 70–74.
Arya, M., Bott, S.R., Shergill, I.S., Ahmed, H.U., Williamson, M. and Patel, H.R. (2006) The metastatic cascade in prostate cancer. Surg. Oncol. 23, 77–83.
Becker, Y. (1992) Anticancer role of dendritic cells (DC) in human and experimental cancers – a review. Anticancer Res. 12, 511–520.
Catalona, W.J., Partin, A.W., Slawin, K.M., Brawer, M.K., Flanigan, R.C., Patel, A., Richie, J.P., deKernion, J.B., Walsh, P.C., Scardino, P.T., Lange, P.H., Subong, E.N., Parson, R.E., Gasior, G.H., Loveland, K.G. and Southwick, P.C. (1998) Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 279, 1542–1547.
Christensson, A., Bjork, T., Nilsson, O., Dahlen, U., Matikainen, M.T., Cockett, A.T., Abrahamsson, P.A. and Lilja, H. (1993) Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J. Urol. 150, 100–105.
Christensson, A., Laurell, C.B. and Lilja, H. (1990) Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur. J. Biochem. 194, 755–763.
Colaco, C.A. (1999a) DC-based cancer immunotherapy: the sequel. Immunol. Today 20, 197–198.
Colaco, C.A. (1999b) Why are dendritic cells central to cancer immunotherapy? Mol. Med. Today 5, 14–17.
Comuzzi, B. and Sadar, M.D. (2006) Proteomic analyses to identify novel therapeutic targets for the treatment of advanced prostate cancer. Cell Sci. 3, 61–81.
Diamandis, E.P. and Yu, H. (1997) Nonprostatic sources of prostate-specific antigen. Urol. Clin. North. Am. 24, 275–282.
Elabbady, A.A. and Khedr, M.M. (2006) Free/total PSA ratio can help in the prediction of high gleason score prostate cancer in men with total serum prostate specific antigen (PSA) of 3-10 ng/ml. Int. Urol. Nephrol. 38, 553–557.
Frassica, F.J., Gitelis, S. and Sim, F.H. (1992) Metastatic bone disease: general principles, pathophysiology, evaluation, and biopsy. Instr. Course Lect. 41, 293–300.
Hall, C.L., Bafico, A., Dai, J., Aaronson, S.A. and Keller, E.T. (2005) Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res. 65, 7554–7560.
Harris, D.T., Matyas, G.R., Gomella, L.G., Talor, E., Winship, M.D., Spitler, L.E. and Mastrangelo, M.J. (1999) Immunologic approaches to the treatment of prostate cancer. Semin. Oncol. 26, 439–447.
Healy, C.G., Simons, J.W., Carducci, M.A., DeWeese, T.L., Bartkowski, M., Tong, K.P. and Bolton, W.E. (1998) Impaired expression and function of signal-transducing zeta chains in peripheral T cells and natural killer cells in patients with prostate cancer. Cytometry 32, 109–119.
Herr, H.W. (1980) Suppressor cells in immunodepressed bladder and prostate cancer patients. J. Urol. 123, 635–639.
Huang, A.Y.C., Golumbek, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D. and Levitsky, H. (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264, 961–965.
Ivshina, A.V., Zhumagazin Zh, D., Zabotina, T.N., Matveev, B.P. and Kadagidze, Z.G. (1995) Effect of the spread of the process and treatment on the phenotype of peripheral blood lymphocytes in patients with prostatic cancer. Urologiia. i. Nefrologiia 9, 36–38.
Jung, K., Brux, B., Lein, M., Rudolph, B., Kristiansen, G., Hauptmann, S., Schnorr, D., Loening, S.A. and Sinha, P. (2000) Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications. Clin. Chem. 46, 47–54.
Landis, S.H., Murray, T., Bolden, S. and Wingo, P.A. (1999) Cancer statistics, 1999. CA Cancer J. Clin. 49, 8–31.
Li, N., Qin, H., Li, X., Zhou, C., Wang, D., Ma, W., Lin, C., Zhang, Y., Wang, S. and Zhang, S. (2006) Potent systemic antitumor immunity induced by vaccination with chemotactic-prostate tumor associated antigen gene-modified tumor cell and blockade of B7-H1. J. Clin. Immunol. 27, 117–130.
Lilja, H. (1993) Structure, function, and regulation of the enzyme activity of prostate- specific antigen. World J. Urol. 11, 188–191.
Lotze, M.T. (1997) Getting to the source: dendritic cells as therapeutic reagents for the treatment of patients with cancer [editorial; comment]. Ann. Surg. 226, 1–5.
McGregor, A.R., Moore, M.L., Bailey, R.R., Robson, R.A. and Lynn, K.L. (1990) Disseminated prostatic carcinoma presenting with acute interstitial nephritis and microangiopathic haemolytic anaemia. Aust. N. Z. J. Med. 20, 170–172.
Mohamedali, K.A., Poblenz, A.T., Sikes, C.R., Navone, N.M., Thorpe, P.E., Darnay, B.G. and Rosenblum, M.G. (2006) Inhibition of prostate tumor growth and bone remodeling by the vascular targeting agent VEGF121/rGel. Cancer Res. 66, 10919–10928.
Oesterling, J.E. (1991) Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J. Urol. 145, 907–923.
Polascik, T.J., Oesterling, J.E. and Partin, A.W. (1999) Prostate specific antigen: a decade of discovery–what we have learned and where we are going. J. Urol. 162, 293–306.
Ragde, H., Cavanagh, W.A. and Tjoa, B.A. (2004) Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer. J. Urol. 172, 2532–2538.
Salgaller, M.L., Lodge, P.A., McLean, J.G., Tjoa, B.A., Loftus, D.J., Ragde, H., Kenny, G.M., Rogers, M., Boynton, A.L. and Murphy, G.P. (1998) Report of immune monitoring of prostate cancer patients undergoing T cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen. Prostate 35, 144–151.
Shamdas, G.J., Ahmann, F.R., Matzner, M.B. and Ritchie, J.M. (1993) Leukoerythroblastic anemia in metastatic prostate cancer. Clinical and prognostic significance in patients with hormone-refractory disease. Cancer 71, 3594–3600.
Shurin, G.V., Aalamian, M., Pirtskhalaishvili, G., Bykovskaia, S., Huland, E., Huland, H. and Shurin, M.R. (2001) Human prostate cancer blocks the generation of endritic cells from CD34+ hematopoietic progenitors. Eur. Urol. 39 (suppl), 37–40.
Shurin, M.R. (1996) Dendritic cells presenting tumor antigen. Cancer Immunol. Immunother. 43, 158–164.
Simons, J.W., Mikhak, B., Chang, J.F., DeMarzo, A.M., Carducci, M.A., Lim, M., Weber, C.E., Baccala, A.A., Goemann, M.A., Clift, S.M., Ando, D.G., Levitsky, H.I., Cohen, L.K., Sanda, M.G., Mulligan, R.C., Partin, A.W., Carter, H.B., Piantadosi, S., Marshall, F.F. and Nelson, W.G. (1999) Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res. 59, 5160–5168.
Slovin, S.F., Kelly, W.K. and Scher, H.I. (1998) Immunological approaches for the treatment of prostate cancer. Semin. Urol. Oncol. 16, 53–59.
Speiser, D.E., Miranda, R., Zakarian, A., Bachmann, M.F., McKall-Faienza, K., Odermatt, B., Hanahan, D., Zinkernagel, R.M. and Ohashi, P.S. (1997) Self antigens expressed by soild tumors do not efficiently stimulate naïve or activated T cells: implications for immunotherapy. J. Exp. Med. 186, 645–653.
Stamey, T.A., Yang, N., Hay, A.R., McNeal, J.E., Freiha, F.S. and Redwine, E. (1987) Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N. Engl. J. Med. 317, 909–916.
Stephan, C., Jung, K., Lein, M., Sinha, P., Schnorr, D. and Loening, S.A. (2000) Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer. Cancer Epidemiol. Biomarkers Prev. 9, 1133–1147.
Troy, A., Davidson, P., Atkinson, C. and Hart, D. (1998) Phenotypic characterization of the dendritic cell infiltrate in prostate cancer. J. Urol. 160, 214–219.
Troy, A., Davidson, P., Atkinson, C. and Hart, D. (1999) Renal cell carcinoma and prostate cancer inhibit dendritic cell activation. Aust. N. Z. J. Surg. 69, A111–A112.
Williams, S.A., Singh, P., Isaacs, J.T. and Denmeade, S.R. (2006) Does PSA play a role as a promoting agent during the initiation and/or progression of prostate cancer? Prostate 67, 312–329.
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Aalamian-Matheis, M., Chatta, G.S., Shurin, M.R., Huland, E., Huland, H., Shurin, G.V. (2007). Inhibition of Dendritic Cell Generation and Function by Serum from Prostate Cancer Patients: Correlation with Serum-Free PSA. In: Shurin, M.R., Smolkin, Y.S. (eds) Immune-Mediated Diseases. Advances in Experimental Medicine and Biology, vol 601. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72005-0_18
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DOI: https://doi.org/10.1007/978-0-387-72005-0_18
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