Skip to main content
Top
Published in: Annals of Hematology 5/2007

01-05-2007 | Original Article

Upregulation of antigen-processing machinery components at mRNA level in acute lymphoblastic leukemia cells after CD40 stimulation

Authors: Włodzimierz Łuczyński, Oksana Kowalczuk, Elżbieta Iłendo, Anna Stasiak-Barmuta, Maryna Krawczuk-Rybak

Published in: Annals of Hematology | Issue 5/2007

Login to get access

Abstract

The development of immunotherapy in hematologic malignancies has been observed in the last few years. One of the approaches is the use of cancer vaccines based on leukemia-derived dendritic cells (DC). Recent studies from our laboratory and other laboratories have shown that CD40 stimulation improves leukemia cells immunogenicity and generates an antitumor immune response. The design of future cancer vaccines requires the knowledge concerning the function of dendritic cells including antigen processing. The aim of our present study was the assessment of antigen-processing machinery (APM) components in acute lymphoblastic leukemia (ALL) cells before and after CD40 stimulation at messenger RNA (mRNA) level. Twenty-five children with ALL were enrolled into the study. Leukemic cells were stimulated (or not) with CD40L and IL-4. Elements of the antigen-processing machinery (MB1, LMP2, LMP7, LMP10, TAP1, TAP2, calnexin, calreticulin, tapasin, ERp57, zeta, delta) were determined by real-time PCR technique. The expression of important costimulatory and adhesion molecules considered as DC markers (CD40, CD54, CD80, CD83, CD86) were determined at the mRNA (PCR) and protein (flow cytometry) levels. The following are the results of our study: (1) We noted an upregulation of all costimulatory and adhesion molecules at the mRNA and protein levels in ALL cells after the culture; (2) the significant rise in expression of nearly all APM components after CD40 stimulation was observed. This confirms specific stimulation of the antigen-processing system in ALL cells by CD40L. Future work should focus on the clinical significance of these findings for immunotherapy in leukemias.
Literature
1.
go back to reference D’Amico G, Marin V, Biondi A (2004) Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor acute lymphoblastic leukaemia. Best Pract Res Clin Haematol 17:465–477PubMedCrossRef D’Amico G, Marin V, Biondi A (2004) Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor acute lymphoblastic leukaemia. Best Pract Res Clin Haematol 17:465–477PubMedCrossRef
2.
go back to reference Łuczyński W, Stasiak-Barmuta A, Iłendo E, Krawczuk-Rybak M, Malinowska I, Mitura-Lesiuk M, Parfieńczyk A, Szymański A (2006) CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells. Acta Biochim Pol 53:377–382 Łuczyński W, Stasiak-Barmuta A, Iłendo E, Krawczuk-Rybak M, Malinowska I, Mitura-Lesiuk M, Parfieńczyk A, Szymański A (2006) CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells. Acta Biochim Pol 53:377–382
3.
go back to reference D’Amico G, Vulcano M, Bugarin C, Bianchi G, Pirovano G, Bonamino M, Marin V, Allavena P, Biagi E, Biondi A (2004) CD40 activation of BCP–ALL cells generates IL-10-producing, IL-12 defective APCs that induce allogeneic T-cell anergy. Blood 104:744–751PubMedCrossRef D’Amico G, Vulcano M, Bugarin C, Bianchi G, Pirovano G, Bonamino M, Marin V, Allavena P, Biagi E, Biondi A (2004) CD40 activation of BCP–ALL cells generates IL-10-producing, IL-12 defective APCs that induce allogeneic T-cell anergy. Blood 104:744–751PubMedCrossRef
4.
go back to reference Łuczyński W, Iłendo E, Kovalchuk O, Krawczuk-Rybak M, Malinowska I, Kołtan A, Szczepański T, Wysocka J, Jaworowski R, Olejnik I, Chyczewski L, Matysiak M, Wysocki M, Sońta-Jakimczyk D, Wieczorek M (2006) Acute lymphoblastic leukemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation. Scand J Clin Lab Invest 66:695–704 Łuczyński W, Iłendo E, Kovalchuk O, Krawczuk-Rybak M, Malinowska I, Kołtan A, Szczepański T, Wysocka J, Jaworowski R, Olejnik I, Chyczewski L, Matysiak M, Wysocki M, Sońta-Jakimczyk D, Wieczorek M (2006) Acute lymphoblastic leukemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation. Scand J Clin Lab Invest 66:695–704
5.
go back to reference Abele R, Tampe R (2006) Modulation of the antigen transport machinery TAP by friends and enemies. FEBS Lett 580:1156–1163PubMedCrossRef Abele R, Tampe R (2006) Modulation of the antigen transport machinery TAP by friends and enemies. FEBS Lett 580:1156–1163PubMedCrossRef
6.
go back to reference Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ, Seliger B (2001) Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol 19:1211–1220PubMed Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ, Seliger B (2001) Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol 19:1211–1220PubMed
7.
go back to reference Atkins D, Ferrone S, Schmahl GE, Storkel S, Seliger B (2004) Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma? J Urol 171:885–889PubMedCrossRef Atkins D, Ferrone S, Schmahl GE, Storkel S, Seliger B (2004) Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma? J Urol 171:885–889PubMedCrossRef
8.
go back to reference Romero JM, Jimenez P, Cabrera T, Cozar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F (2005) Coordinated downregulation of the antigen presentation machinery and HLA class I/beta2-microglobulin complex is responsible for HLA–ABC loss in bladder cancer. Int J Cancer 113:605–610PubMedCrossRef Romero JM, Jimenez P, Cabrera T, Cozar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F (2005) Coordinated downregulation of the antigen presentation machinery and HLA class I/beta2-microglobulin complex is responsible for HLA–ABC loss in bladder cancer. Int J Cancer 113:605–610PubMedCrossRef
9.
go back to reference Facoetti A, Nano R, Zelini P, Morbini P, Benericetti E, Ceroni M, Campoli M, Ferrone S (2005) Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res 11:8304–8311PubMedCrossRef Facoetti A, Nano R, Zelini P, Morbini P, Benericetti E, Ceroni M, Campoli M, Ferrone S (2005) Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res 11:8304–8311PubMedCrossRef
10.
go back to reference Frisan T, Zhang QJ, Levitskaya J, Coram M, Kurilla MG, Masucci MG (1996) Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt’s lymphoma cells. Int J Cancer 68:251–258PubMedCrossRef Frisan T, Zhang QJ, Levitskaya J, Coram M, Kurilla MG, Masucci MG (1996) Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt’s lymphoma cells. Int J Cancer 68:251–258PubMedCrossRef
11.
go back to reference Dutta N, Gupta A, Mazumder DN, Banerjee S (2006) Down-regulation of locus-specific human lymphocyte antigen class I expression in Epstein–Barr virus-associated gastric cancer: implication for viral-induced immune evasion. Cancer 106:1685–1693PubMedCrossRef Dutta N, Gupta A, Mazumder DN, Banerjee S (2006) Down-regulation of locus-specific human lymphocyte antigen class I expression in Epstein–Barr virus-associated gastric cancer: implication for viral-induced immune evasion. Cancer 106:1685–1693PubMedCrossRef
12.
go back to reference Ressing ME, Keating SE, van Leeuwen D, Koppers-Lalic D, Pappworth IY, Wiertz EJ, Rowe M (2005) Impaired transporter associated with antigen processing-dependent peptide transport during productive EBV infection. J Immunol 174:6829–6838PubMed Ressing ME, Keating SE, van Leeuwen D, Koppers-Lalic D, Pappworth IY, Wiertz EJ, Rowe M (2005) Impaired transporter associated with antigen processing-dependent peptide transport during productive EBV infection. J Immunol 174:6829–6838PubMed
13.
go back to reference Claus JA, Brady MT, Lee J, Donohue KA, Sait SN, Ferrone S, Wetzler M (2006) T-cell activation by t(9;22) acute lymphoblastic leukemia-derived dendritic cells is associated with increased tapasin expression. Cancer Immunol Immunotheras 55:160–165CrossRef Claus JA, Brady MT, Lee J, Donohue KA, Sait SN, Ferrone S, Wetzler M (2006) T-cell activation by t(9;22) acute lymphoblastic leukemia-derived dendritic cells is associated with increased tapasin expression. Cancer Immunol Immunotheras 55:160–165CrossRef
14.
go back to reference Ghia P, Transdico P, Veiga JP, Schaniel C, Sallusto F, Matsushima K, Sallan SE, Rolink AG, Mantovani A, Nadler LM, Cardoso AA (2001) Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells. Blood 98:533–540PubMedCrossRef Ghia P, Transdico P, Veiga JP, Schaniel C, Sallusto F, Matsushima K, Sallan SE, Rolink AG, Mantovani A, Nadler LM, Cardoso AA (2001) Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells. Blood 98:533–540PubMedCrossRef
15.
go back to reference Seliger B, Schreiber K, Delp K, Meissner M, Hammers S, Reichert T, Pawlischko K, Tampe R, Huber C (2001) Downregulation of the constitutive tapasin expression on human tumor cells of distinct origin and its transcriptional upregulation by cytokines. Tissue Antigens 57:39–45PubMedCrossRef Seliger B, Schreiber K, Delp K, Meissner M, Hammers S, Reichert T, Pawlischko K, Tampe R, Huber C (2001) Downregulation of the constitutive tapasin expression on human tumor cells of distinct origin and its transcriptional upregulation by cytokines. Tissue Antigens 57:39–45PubMedCrossRef
16.
go back to reference Whiteside TL, Stanson J, Shurin MR, Ferrone S (2004) Antigen-processing machinery in human dendritic cells: up-regulation by maturation and down-regulation by tumor cells. J Immunol 173:1526–1534PubMed Whiteside TL, Stanson J, Shurin MR, Ferrone S (2004) Antigen-processing machinery in human dendritic cells: up-regulation by maturation and down-regulation by tumor cells. J Immunol 173:1526–1534PubMed
17.
go back to reference Tourkova IL, Shurin GV, Chatta GS, Perez L, Finke J, Whiteside TL, Ferrone S, Shurin MR (2005) Restoration by IL-15 of MHC class I antigen-processing machinery in human dendritic cells inhibited by tumor-derived gangliosides. J Immunol 175:3045–3052PubMed Tourkova IL, Shurin GV, Chatta GS, Perez L, Finke J, Whiteside TL, Ferrone S, Shurin MR (2005) Restoration by IL-15 of MHC class I antigen-processing machinery in human dendritic cells inhibited by tumor-derived gangliosides. J Immunol 175:3045–3052PubMed
18.
go back to reference Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V (2005) Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene 24:4634–4644PubMedCrossRef Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V (2005) Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene 24:4634–4644PubMedCrossRef
19.
go back to reference Satoh E, Mabuchi T, Satoh H, Asahara T, Nukui H, Naganuma H (2006) Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon–gamma and –beta. J Neurosurg 104:264–271PubMed Satoh E, Mabuchi T, Satoh H, Asahara T, Nukui H, Naganuma H (2006) Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon–gamma and –beta. J Neurosurg 104:264–271PubMed
20.
go back to reference Lopez-Albaitero A, Nayak JV, Ogino T, Machandia A, Gooding W, de Leo AB, Ferrone S, Ferris RL (2006) Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J Immunol 176:3402–3409PubMed Lopez-Albaitero A, Nayak JV, Ogino T, Machandia A, Gooding W, de Leo AB, Ferrone S, Ferris RL (2006) Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J Immunol 176:3402–3409PubMed
21.
go back to reference 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 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
22.
go back to reference Alimonti J, Zhang QJ, Gabathuler R, Reid G, Chen SS, Jefferies WA (2000) TAP expression provides a general method for improving the recognition of malignant cells in vivo. Nat Biotechnol 18:515–520PubMedCrossRef Alimonti J, Zhang QJ, Gabathuler R, Reid G, Chen SS, Jefferies WA (2000) TAP expression provides a general method for improving the recognition of malignant cells in vivo. Nat Biotechnol 18:515–520PubMedCrossRef
23.
go back to reference Lin CT, Chang TC, Chao A, Dzeng E, Soong YK, Hung CF, Lai CH (2005) Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin. J Biomed Sci 12:279–287PubMedCrossRef Lin CT, Chang TC, Chao A, Dzeng E, Soong YK, Hung CF, Lai CH (2005) Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin. J Biomed Sci 12:279–287PubMedCrossRef
24.
go back to reference Yang T, Lapinski PE, Zhao H, Zhou Q, Zhang H, Raghavan M, Liu Y, Zheng P (2005) A rare transporter associated with antigen processing polymorphism overpresented in HLAlow colon cancer reveals the functional significance of the signature domain in antigen processing. Clin Cancer Res 11:3614–3623PubMedCrossRef Yang T, Lapinski PE, Zhao H, Zhou Q, Zhang H, Raghavan M, Liu Y, Zheng P (2005) A rare transporter associated with antigen processing polymorphism overpresented in HLAlow colon cancer reveals the functional significance of the signature domain in antigen processing. Clin Cancer Res 11:3614–3623PubMedCrossRef
25.
go back to reference Agrawal S, Reemtsma K, Bagiella E, Oluwole SF, Braunstein NS (2004) Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma. Cell Immunol 228:130–137PubMedCrossRef Agrawal S, Reemtsma K, Bagiella E, Oluwole SF, Braunstein NS (2004) Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma. Cell Immunol 228:130–137PubMedCrossRef
26.
go back to reference Norbury CC, Princiotta MF, Bacik I, Brutkiewicz RR, Wood P, Elliott T, Bennink JR, Yewdell JW (2001) Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. J Immunol 166:4355–4362PubMed Norbury CC, Princiotta MF, Bacik I, Brutkiewicz RR, Wood P, Elliott T, Bennink JR, Yewdell JW (2001) Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. J Immunol 166:4355–4362PubMed
27.
go back to reference Dissanayake SK, Tuera N, Ostrand-Rosenberg S (2005) Presentation of endogenously synthesized MHC class II-restricted epitopes by MHC class II cancer vaccines is independent of transporter associated with Ag processing and the proteasome. J Immunol 174:1811–1819PubMed Dissanayake SK, Tuera N, Ostrand-Rosenberg S (2005) Presentation of endogenously synthesized MHC class II-restricted epitopes by MHC class II cancer vaccines is independent of transporter associated with Ag processing and the proteasome. J Immunol 174:1811–1819PubMed
28.
go back to reference van Hall T, Wolpert EZ, van Veelen P, Laban S, van der Veer M, Roseboom M, Bres S, Grufman P, de Ru A, Meiring H, deJong A, Franken K, Teixeira A, Valentijn R, Drijfhout JW, Konig F, Camps M, Ossendorp F, Karre K, Ljunggren HG, Melief CJ, Offringa R (2006) Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Nat Med 12:417–424PubMedCrossRef van Hall T, Wolpert EZ, van Veelen P, Laban S, van der Veer M, Roseboom M, Bres S, Grufman P, de Ru A, Meiring H, deJong A, Franken K, Teixeira A, Valentijn R, Drijfhout JW, Konig F, Camps M, Ossendorp F, Karre K, Ljunggren HG, Melief CJ, Offringa R (2006) Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Nat Med 12:417–424PubMedCrossRef
29.
go back to reference Turnquist HR, Kohlgraf KG, McIlhaney MM, Mosley RL, Hollingsworth MA, Solheim JC (2004) Tapasin decreases immune responsiveness to a model tumor antigen. J Clin Immunol 24:462–470PubMedCrossRef Turnquist HR, Kohlgraf KG, McIlhaney MM, Mosley RL, Hollingsworth MA, Solheim JC (2004) Tapasin decreases immune responsiveness to a model tumor antigen. J Clin Immunol 24:462–470PubMedCrossRef
Metadata
Title
Upregulation of antigen-processing machinery components at mRNA level in acute lymphoblastic leukemia cells after CD40 stimulation
Authors
Włodzimierz Łuczyński
Oksana Kowalczuk
Elżbieta Iłendo
Anna Stasiak-Barmuta
Maryna Krawczuk-Rybak
Publication date
01-05-2007
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 5/2007
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-007-0256-z

Other articles of this Issue 5/2007

Annals of Hematology 5/2007 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

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.

Developed by: Springer Medicine