Clinical Cancer Research Joint Metastasis Research Society-AACR Conference on Metastasis Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Álvaro, T.
Right arrow Articles by Piris, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Álvaro, T.
Right arrow Articles by Piris, M. A.
Clinical Cancer Research Vol. 11, 1467-1473, February 2005
© 2005 American Association for Cancer Research

Imaging, Diagnosis, Prognosis

Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells

Tomás Álvaro1, Marylène Lejeune1, Ma Teresa Salvadó1, Ramón Bosch1, Juan F. García2, Joaquín Jaén1, Alison H. Banham5, Giovanna Roncador3, Carlos Montalbán4 and Miguel A. Piris2

1 Department of Pathology, Hospital Verge de la Cinta, Tortosa, Spain; 2 Molecular Pathology Programme and 3 Monoclonal Antibodies Unit, Centro Nacional de Investigaciones Oncologicas; 4 Department of Internal Medicine, Hospital Ramon y Cajal, Madrid, Spain; and 5 Nuffield Department of Clinical Laboratory Sciences, Leukaemia Research Fund Immunodiagnostics Unit, John Radcliffe Hospital, Oxford, United Kingdom

Requests for reprints: Tomás Álvaro-Naranjo, Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/ Esplanetes n° 14, 43500-Tortosa, Spain. Phone: 34-977-519104; Fax: 34-977-519104; E-mail: talvaro.htvc.ics{at}gencat.net.

Purpose: Recent studies of Hodgkin's lymphoma (HL) have suggested that the presence of regulatory T cells in the reactive background may explain the inhibition of the antitumoral host immune response observed in these patients. This study aimed to assess the relevance of regulatory T cells and CTLs present in the background of HL samples in the prognosis of a series of classic HL (cHL) patients.

Experimental Design: Expression of granzyme B and TIA-1 (markers for CTL) and FOXP3 (a marker for regulatory T cells) were evaluated independently by immunohistochemistry in tissue microarrays of 257 cHL patients and correlated with patient outcome.

Results: The combined influence of the presence of FOXP3+ and TIA-1+ cells distinguished three risk groups of patients with 5-year overall survival of 100%, 88%, and 73%. The presence of a small number of FOXP3+ cells and a high proportion of TIA-1+ cells in the infiltrate represent an independent prognostic factor that negatively influenced event-free survival and disease-free survival in cHL. Compared with the features at diagnosis, relapsed samples tended to have more TIA-1+ cells and a lower proportion of FOXP3+ cells in the reactive background.

Conclusions: These data suggest that low infiltration of FOXP3+ cells in conjunction with high infiltration of TIA-1+ cells in cHL may represent biological markers predicting an unfavorable outcome. Moreover, the variation of these markers over the course of the disease implies a possible role for them in the progression of HL cases.

Key Words: Immunohistochemistry • CTL • FOXP3 • immune response • survival




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
K. R.N. Baumforth, A. Birgersdotter, G. M. Reynolds, W. Wei, G. Kapatai, J. R. Flavell, E. Kalk, K. Piper, S. Lee, L. Machado, et al.
Expression of the Epstein-Barr Virus-Encoded Epstein-Barr Virus Nuclear Antigen 1 in Hodgkin's Lymphoma Cells Mediates Up-Regulation of CCL20 and the Migration of Regulatory T Cells
Am. J. Pathol., July 1, 2008; 173(1): 195 - 204.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Mittal, N. A. Marshall, L. Duncan, D. J. Culligan, R. N. Barker, and M. A. Vickers
Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma
Blood, June 1, 2008; 111(11): 5359 - 5370.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Yamamoto, M. Nishikori, T. Kitawaki, T. Sakai, M. Hishizawa, M. Tashima, T. Kondo, K. Ohmori, M. Kurata, T. Hayashi, et al.
PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma
Blood, March 15, 2008; 111(6): 3220 - 3224.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Alvaro, M. Lejeune, J. F. Garcia, Ma. T. Salvado, C. Lopez, R. Bosch, J. Jaen, P. Escriva, and L. E. Pons
Tumor-Infiltrated Immune Response Correlates with Alterations in the Apoptotic and Cell Cycle Pathways in Hodgkin and Reed-Sternberg Cells
Clin. Cancer Res., February 1, 2008; 14(3): 685 - 691.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
A. Tzankov, C. Meier, P. Hirschmann, P. Went, S. A. Pileri, and S. Dirnhofer
Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma
Haematologica, February 1, 2008; 93(2): 193 - 200.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Haas, L. Schopp, B. Storch-Hagenlocher, B. Fritzsching, C. Jacobi, L. Milkova, B. Fritz, A. Schwarz, E. Suri-Payer, M. Hensel, et al.
Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis
Blood, January 15, 2008; 111(2): 761 - 766.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
C. Atayar, A. van den Berg, T. Blokzijl, M. Boot, R. D Gascoyne, L. Visser, and S. Poppema
Hodgkin's lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments
J. Clin. Pathol., October 1, 2007; 60(10): 1092 - 1097.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
T. Tanijiri, T. Shimizu, K. Uehira, T. Yokoi, H. Amuro, H. Sugimoto, Y. Torii, K. Tajima, T. Ito, R. Amakawa, et al.
Hodgkin's Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells
J. Leukoc. Biol., September 1, 2007; 82(3): 576 - 584.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Strauss, C. Bergmann, M. Szczepanski, W. Gooding, J. T. Johnson, and T. L. Whiteside
A Unique Subset of CD4+CD25highFoxp3+ T Cells Secreting Interleukin-10 and Transforming Growth Factor-{beta}1 Mediates Suppression in the Tumor Microenvironment
Clin. Cancer Res., August 1, 2007; 13(15): 4345 - 4354.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Diepstra, G. W. van Imhoff, H. E. Karim-Kos, A. van den Berg, G. J. te Meerman, M. Niens, I. M. Nolte, E. Bastiaannet, M. Schaapveld, E. Vellenga, et al.
HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma
J. Clin. Oncol., July 20, 2007; 25(21): 3101 - 3108.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. Yakirevich and M. B. Resnick
Regulatory T Lymphocytes: Pivotal Components of the Host Antitumor Response
J. Clin. Oncol., June 20, 2007; 25(18): 2506 - 2508.
[Full Text] [PDF]

Home page
 JCOHome page
Q. Gao, S.-J. Qiu, J. Fan, J. Zhou, X.-Y. Wang, Y.-S. Xiao, Y. Xu, Y.-W. Li, and Z.-Y. Tang
Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection
J. Clin. Oncol., June 20, 2007; 25(18): 2586 - 2593.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
T. Alvaro, M. Lejeune, M.-T. Salvado, C. Lopez, P. Escriva, J. Jaen, R. Bosch, and L. E. Pons
In Reply
J. Clin. Oncol., April 1, 2007; 25(10): 1291 - 1292.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
S. P. Hilchey, A. De, L. M. Rimsza, R. B. Bankert, and S. H. Bernstein
Follicular Lymphoma Intratumoral CD4+CD25+GITR+ Regulatory T Cells Potently Suppress CD3/CD28-Costimulated Autologous and Allogeneic CD8+CD25- and CD4+CD25- T Cells
J. Immunol., April 1, 2007; 178(7): 4051 - 4061.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. A. Siddiqui, X. Frigola, S. Bonne-Annee, M. Mercader, S. M. Kuntz, A. E. Krambeck, S. Sengupta, H. Dong, J. C. Cheville, C. M. Lohse, et al.
Tumor-Infiltrating Foxp3-CD4+CD25+ T Cells Predict Poor Survival in Renal Cell Carcinoma
Clin. Cancer Res., April 1, 2007; 13(7): 2075 - 2081.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
R. F. Ambinder
Epstein-Barr Virus and Hodgkin Lymphoma
Hematology, January 1, 2007; 2007(1): 204 - 209.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
T. Alvaro, M. Lejeune, M.-T. Salvado, C. Lopez, J. Jaen, R. Bosch, and L. E. Pons
Immunohistochemical Patterns of Reactive Microenvironment Are Associated With Clinicobiologic Behavior in Follicular Lymphoma Patients
J. Clin. Oncol., December 1, 2006; 24(34): 5350 - 5357.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. J. Bates, S. B. Fox, C. Han, R. D. Leek, J. F. Garcia, A. L. Harris, and A. H. Banham
Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse
J. Clin. Oncol., December 1, 2006; 24(34): 5373 - 5380.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Miller, K. Lundberg, V. Ozenci, A. H. Banham, M. Hellstrom, L. Egevad, and P. Pisa
CD4+CD25high T Cells Are Enriched in the Tumor and Peripheral Blood of Prostate Cancer Patients
J. Immunol., November 15, 2006; 177(10): 7398 - 7405.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. M. Lee, A. J. Clear, M. Calaminici, A. J. Davies, S. Jordan, F. MacDougall, J. Matthews, A. J. Norton, J. G. Gribben, T. A. Lister, et al.
Number of CD4+ Cells and Location of Forkhead Box Protein P3-Positive Cells in Diagnostic Follicular Lymphoma Tissue Microarrays Correlates With Outcome
J. Clin. Oncol., November 1, 2006; 24(31): 5052 - 5059.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Carreras, A. Lopez-Guillermo, B. C. Fox, L. Colomo, A. Martinez, G. Roncador, E. Montserrat, E. Campo, and A. H. Banham
High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma
Blood, November 1, 2006; 108(9): 2957 - 2964.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. K. Gandhi, E. Lambley, J. Duraiswamy, U. Dua, C. Smith, S. Elliott, D. Gill, P. Marlton, J. Seymour, and R. Khanna
Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients
Blood, October 1, 2006; 108(7): 2280 - 2289.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Hiraoka, K. Onozato, T. Kosuge, and S. Hirohashi
Prevalence of FOXP3+ Regulatory T Cells Increases During the Progression of Pancreatic Ductal Adenocarcinoma and Its Premalignant Lesions.
Clin. Cancer Res., September 15, 2006; 12(18): 5423 - 5434.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Beyer and J. L. Schultze
Regulatory T cells in cancer
Blood, August 1, 2006; 108(3): 804 - 811.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Sanchez-Aguilera, C. Montalban, P. de la Cueva, L. Sanchez-Verde, M. M. Morente, M. Garcia-Cosio, J. Garcia-Larana, C. Bellas, M. Provencio, V. Romagosa, et al.
Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma
Blood, July 15, 2006; 108(2): 662 - 668.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Beyer, M. Kochanek, T. Giese, E. Endl, M. R. Weihrauch, P. A. Knolle, S. Classen, and J. L. Schultze
In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma
Blood, May 15, 2006; 107(10): 3940 - 3949.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z.-Z. Yang, A. J. Novak, M. J. Stenson, T. E. Witzig, and S. M. Ansell
Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma
Blood, May 1, 2006; 107(9): 3639 - 3646.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Badoual, S. Hans, J. Rodriguez, S. Peyrard, C. Klein, N. E. H. Agueznay, V. Mosseri, O. Laccourreye, P. Bruneval, W. H. Fridman, et al.
Prognostic Value of Tumor-Infiltrating CD4+ T-Cell Subpopulations in Head and Neck Cancers
Clin. Cancer Res., January 15, 2006; 12(2): 465 - 472.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Dranoff
The Therapeutic Implications of Intratumoral Regulatory T Cells
Clin. Cancer Res., December 1, 2005; 11(23): 8226 - 8229.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Wolf, A. M. Wolf, H. Rumpold, H. Fiegl, A. G. Zeimet, E. Muller-Holzner, M. Deibl, G. Gastl, E. Gunsilius, and C. Marth
The Expression of the Regulatory T Cell-Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer
Clin. Cancer Res., December 1, 2005; 11(23): 8326 - 8331.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2005 by the American Association for Cancer Research.