Cancer Research CR Mantle  Sign up for Cancer Research eTOC's
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 Meeting Abstracts Online

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 Email this article to a friend
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 Valzasina, B.
Right arrow Articles by Colombo, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Valzasina, B.
Right arrow Articles by Colombo, M. P.
[Cancer Research 66, 4488-4495, April 15, 2006]
© 2006 American Association for Cancer Research


Immunology

Tumor-Induced Expansion of Regulatory T Cells by Conversion of CD4+CD25 Lymphocytes Is Thymus and Proliferation Independent

Barbara Valzasina, Silvia Piconese, Cristiana Guiducci and Mario P. Colombo

Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy

Requests for reprints: Mario P. Colombo, Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. Phone: 39-02-2390-2252; Fax: 39-02-2390-2630; E-mail: mario.colombo{at}istitutotumori.mi.it.

The CD25 and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4+CD25+ T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25+ T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4+CD25 T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4+CD25 T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody–mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors. (Cancer Res 2006; 66(8): 4488-95)




This article has been cited by other articles:


Home page
Cancer Res.Home page
P.-Y. Pan, G. Ma, K. J. Weber, J. Ozao-Choy, G. Wang, B. Yin, C. M. Divino, and S.-H. Chen
Immune Stimulatory Receptor CD40 Is Required for T-Cell Suppression and T Regulatory Cell Activation Mediated by Myeloid-Derived Suppressor Cells in Cancer
Cancer Res., January 1, 2010; 70(1): 99 - 108.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
U. Petrausch, S. M. Jensen, C. Twitty, C. H. Poehlein, D. P. Haley, E. B. Walker, and B. A. Fox
Disruption of TGF-{beta} Signaling Prevents the Generation of Tumor-Sensitized Regulatory T Cells and Facilitates Therapeutic Antitumor Immunity
J. Immunol., September 15, 2009; 183(6): 3682 - 3689.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
T. Fujita, K. Teramoto, Y. Ozaki, J. Hanaoka, N. Tezuka, Y. Itoh, T. Asai, S. Fujino, K. Kontani, and K. Ogasawara
Inhibition of Transforming Growth Factor-{beta}-Mediated Immunosuppression in Tumor-Draining Lymph Nodes Augments Antitumor Responses by Various Immunologic Cell Types
Cancer Res., June 15, 2009; 69(12): 5142 - 5150.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
Z. Liu, J. H. Kim, L. D. Falo Jr., and Z. You
Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity
J. Immunol., May 15, 2009; 182(10): 6160 - 6167.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
D. Hirschhorn-Cymerman, G. A. Rizzuto, T. Merghoub, A. D. Cohen, F. Avogadri, A. M. Lesokhin, A. D. Weinberg, J. D. Wolchok, and A. N. Houghton
OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis
J. Exp. Med., May 11, 2009; 206(5): 1103 - 1116.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. Huber, F. R. Stahl, J. Schrader, S. Luth, K. Presser, A. Carambia, R. A. Flavell, S. Werner, M. Blessing, J. Herkel, et al.
Activin A Promotes the TGF-{beta}-Induced Conversion of CD4+CD25- T Cells into Foxp3+ Induced Regulatory T Cells
J. Immunol., April 15, 2009; 182(8): 4633 - 4640.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. Getnet, C. H. Maris, E. L. Hipkiss, J. F. Grosso, T. J. Harris, H.-R. Yen, T. C. Bruno, S. Wada, A. Adler, R. W. Georgantas, et al.
Tumor Recognition and Self-Recognition Induce Distinct Transcriptional Profiles in Antigen-Specific CD4 T Cells
J. Immunol., April 15, 2009; 182(8): 4675 - 4685.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
N Chaput, S Louafi, A Bardier, F Charlotte, J-C Vaillant, F Menegaux, M Rosenzwajg, F Lemoine, D Klatzmann, and J Taieb
Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue
Gut, April 1, 2009; 58(4): 520 - 529.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Curti, S. Trabanelli, V. Salvestrini, M. Baccarani, and R. M. Lemoli
The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology
Blood, March 12, 2009; 113(11): 2394 - 2401.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
K. A. Pilones, N. Kawashima, A. M. Yang, J. S. Babb, S. C. Formenti, and S. Demaria
Invariant Natural Killer T Cells Regulate Breast Cancer Response to Radiation and CTLA-4 Blockade
Clin. Cancer Res., January 15, 2009; 15(2): 597 - 606.
[Abstract] [Full Text] [PDF]


Home page
Anticancer ResHome page
J. HIGASHIJIMA, M. SHIMADA, M. CHIKAKIYO, T. MIYATANI, K. YOSHIKAWA, M. NISHIOKA, T. IWATA, and N. KURITA
Effect of Splenectomy on Antitumor Immune System in Mice
Anticancer Res, January 1, 2009; 29(1): 385 - 393.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Ahmadzadeh, A. Felipe-Silva, B. Heemskerk, D. J. Powell Jr, J. R. Wunderlich, M. J. Merino, and S. A. Rosenberg
FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions
Blood, December 15, 2008; 112(13): 4953 - 4960.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
N. Larmonier, N. Janikashvili, C. J. LaCasse, C. B. Larmonier, J. Cantrell, E. Situ, T. Lundeen, B. Bonnotte, and E. Katsanis
Imatinib Mesylate Inhibits CD4+CD25+ Regulatory T Cell Activity and Enhances Active Immunotherapy against BCR-ABL- Tumors
J. Immunol., November 15, 2008; 181(10): 6955 - 6963.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
Z. Zhao, S. Yu, D. C. Fitzgerald, M. Elbehi, B. Ciric, A. M. Rostami, and G.-X. Zhang
IL-12R{beta}2 Promotes the Development of CD4+CD25+ Regulatory T Cells
J. Immunol., September 15, 2008; 181(6): 3870 - 3876.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
Z. Liu, H. S. Noh, J. Chen, J. H. Kim, L. D. Falo Jr., and Z. You
Potent Tumor-Specific Protection Ignited by Adoptively Transferred CD4+ T Cells
J. Immunol., September 15, 2008; 181(6): 4363 - 4370.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
P. R. Rai, C. D. Cool, J. A. C. King, T. Stevens, N. Burns, R. A. Winn, M. Kasper, and N. F. Voelkel
The Cancer Paradigm of Severe Pulmonary Arterial Hypertension
Am. J. Respir. Crit. Care Med., September 15, 2008; 178(6): 558 - 564.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
S. A. Quezada, K. S. Peggs, T. R. Simpson, Y. Shen, D. R. Littman, and J. P. Allison
Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma
J. Exp. Med., September 1, 2008; 205(9): 2125 - 2138.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
L. Wang, K. Pino-Lagos, V. C. de Vries, I. Guleria, M. H. Sayegh, and R. J. Noelle
Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells
PNAS, July 8, 2008; 105(27): 9331 - 9336.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
S. Piconese, B. Valzasina, and M. P. Colombo
OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection
J. Exp. Med., April 14, 2008; 205(4): 825 - 839.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
N. Larmonier, J. Cantrell, C. LaCasse, G. Li, N. Janikashvili, E. Situ, M. Sepassi, S. Andreansky, and E. Katsanis
Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression
J. Leukoc. Biol., April 1, 2008; 83(4): 1049 - 1059.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Y.-J. Kim, M.-K. Han, and H. E. Broxmeyer
4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells
Blood, February 1, 2008; 111(3): 1378 - 1386.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
E. Degl'Innocenti, M. Grioni, G. Capuano, E. Jachetti, M. Freschi, M. T.S. Bertilaccio, R. Hess-Michelini, C. Doglioni, and M. Bellone
Peripheral T-Cell Tolerance Associated with Prostate Cancer Is Independent from CD4+CD25+ Regulatory T Cells
Cancer Res., January 1, 2008; 68(1): 292 - 300.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. Urzainqui, G. Martinez del Hoyo, A. Lamana, H. de la Fuente, O. Barreiro, I. M. Olazabal, P. Martin, M. K. Wild, D. Vestweber, R. Gonzalez-Amaro, et al.
Functional Role of P-Selectin Glycoprotein Ligand 1/P-Selectin Interaction in the Generation of Tolerogenic Dendritic Cells
J. Immunol., December 1, 2007; 179(11): 7457 - 7465.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
K. G. Elpek, C. Lacelle, N. P. Singh, E. S. Yolcu, and H. Shirwan
CD4+CD25+ T Regulatory Cells Dominate Multiple Immune Evasion Mechanisms in Early but Not Late Phases of Tumor Development in a B Cell Lymphoma Model
J. Immunol., June 1, 2007; 178(11): 6840 - 6848.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
K. N. Couper, D. G. Blount, J. B. de Souza, I. Suffia, Y. Belkaid, and E. M. Riley
Incomplete Depletion and Rapid Regeneration of Foxp3+ Regulatory T Cells Following Anti-CD25 Treatment in Malaria-Infected Mice
J. Immunol., April 1, 2007; 178(7): 4136 - 4146.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Curti, S. Pandolfi, B. Valzasina, M. Aluigi, A. Isidori, E. Ferri, V. Salvestrini, G. Bonanno, S. Rutella, I. Durelli, et al.
Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells
Blood, April 1, 2007; 109(7): 2871 - 2877.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
V. C. Liu, L. Y. Wong, T. Jang, A. H. Shah, I. Park, X. Yang, Q. Zhang, S. Lonning, B. A. Teicher, and C. Lee
Tumor Evasion of the Immune System by Converting CD4+CD25- T Cells into CD4+CD25+ T Regulatory Cells: Role of Tumor-Derived TGF-beta
J. Immunol., March 1, 2007; 178(5): 2883 - 2892.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. Nair, D. Boczkowski, M. Fassnacht, D. Pisetsky, and E. Gilboa
Vaccination against the Forkhead Family Transcription Factor Foxp3 Enhances Tumor Immunity
Cancer Res., January 1, 2007; 67(1): 371 - 380.
[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 Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.