Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells

被引:58
作者
Ai, Weiyun Z. [1 ,2 ,3 ,4 ]
Hou, Ling-Zhou [1 ,2 ,3 ,5 ]
Zeiser, Robert [1 ,2 ,3 ,6 ]
Czerwinski, Debra [1 ,2 ,3 ]
Negrin, Robert S. [1 ,2 ,3 ]
Levy, Ronald [1 ,2 ,3 ]
机构
[1] Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Med, Div Blood & Transplantat, Stanford, CA 94305 USA
[4] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA
[5] Univ Pittsburgh, Dept Med, Div Hematol & Oncol, Pittsburgh, PA USA
[6] Univ Freiburg, Dept Hematol & Oncol, Freiburg, Germany
关键词
tumor microenvironment; immune escape; HEAVY-CHAIN FERRITIN; DENDRITIC CELLS; FOXP3; EXPRESSION; GENE-EXPRESSION; DEPLETION; TUMORS; RECRUITMENT; REJECTION; IMMUNITY; SURVIVAL;
D O I
10.1002/ijc.23881
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There has been accumulating evidence that CD4(+)CD25(+) FoxP3 expressing regulatory T cells (Treg) are highly concentrated in tumors, thereby fostering an immune-privileged microenvironment. Some studies have shown that T-cell receptor (TCR) stimulation can convert conventional T cells into Treg. Follicular lymphoma (FL) It cells can enhance this Treg conversion. We investigated whether FL tumor B cells, as opposed to normal B cells, are unique in their ability to convert effector T cells into Treg. We found that tumor B cells alone, without artificial TCR stimulation, could induce conventional T cells to express FoxP3 and to acquire regulatory function. In contrast to their malignant counterpart, normal It cells did not induce Treg conversion. Treg conversion was independent of the T cell background, as T cells isolated from FL or normal peripheral blood were equally susceptible to being converted by tumor B cells. Our study provides evidence for a tumor-specific mechanism by which FL tumor cells promote immune escape through the induction of Treg. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:239 / 244
页数:6
相关论文
共 44 条
[1]   In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma [J].
Beyer, Marc ;
Kochanek, Matthias ;
Giese, Thomas ;
Endl, Elmar ;
Weihrauch, Martin R. ;
Knolle, Percy A. ;
Classen, Sabine ;
Schultze, Joachim L. .
BLOOD, 2006, 107 (10) :3940-3949
[2]   Prognostic significance of host immune gene polymorphisms, in follicular lymphoma survival [J].
Cerhan, James R. ;
Wang, Sophia ;
Maurer, Matthew J. ;
Ansell, Stephen M. ;
Geyer, Susan M. ;
Cozen, Wendy ;
Morton, Lindsay M. ;
Davis, Scott ;
Severson, Richard K. ;
Rothman, Nathaniel ;
Lynch, Charles F. ;
Wacholder, Sholom ;
Chanock, Stephen J. ;
Habermann, Thomas M. ;
Hartge, Patricia .
BLOOD, 2007, 109 (12) :5439-5446
[3]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[4]   Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells [J].
Dannull, J ;
Su, Z ;
Rizzieri, D ;
Yang, BK ;
Coleman, D ;
Yancey, D ;
Zhang, AJ ;
Dahm, P ;
Chao, N ;
Gilboa, E ;
Vieweg, J .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (12) :3623-3633
[5]   Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells [J].
Dave, SS ;
Wright, G ;
Tan, B ;
Rosenwald, A ;
Gascoyne, RD ;
Chan, WC ;
Fisher, RI ;
Braziel, RM ;
Rimsza, LM ;
Grogan, TM ;
Miller, TP ;
LeBlanc, M ;
Greiner, TC ;
Weisenburger, DD ;
Lynch, JC ;
Vose, J ;
Armitage, JO ;
Smeland, EB ;
Kvaloy, S ;
Holte, H ;
Delabie, J ;
Connors, JM ;
Lansdorp, PM ;
Ouyang, Q ;
Lister, TA ;
Davies, AJ ;
Norton, AJ ;
Muller-Hermelink, HK ;
Ott, G ;
Campo, E ;
Montserrat, E ;
Wilson, WH ;
Jaffe, ES ;
Simon, R ;
Yang, LM ;
Powell, J ;
Zhao, H ;
Goldschmidt, N ;
Chiorazzi, M ;
Staudt, LM .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (21) :2159-2169
[6]  
FARINA P, 2007, AM SOC HEMATOL ANN M, V110, pA112
[7]   Analysis of multiple biomarkers, shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL) [J].
Farinha, P ;
Masoudi, H ;
Skinnider, BF ;
Shumansky, K ;
Spinelli, JJ ;
Gill, K ;
Klasa, R ;
Voss, N ;
Connors, JM ;
Gascoyne, RD .
BLOOD, 2005, 106 (06) :2169-2174
[8]  
Gavin MA, 2006, P NATL ACAD SCI USA, V103, P6659, DOI 10.1073/pnas.0509484103
[9]  
Ghia P, 2002, EUR J IMMUNOL, V32, P1403, DOI 10.1002/1521-4141(200205)32:5<1403::AID-IMMU1403>3.0.CO
[10]  
2-Y