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

International Journal of Cancer - Tập 124 Số 1 - Trang 239-244 - 2009
Weiyun Z. Ai1,2, Jing‐Zhou Hou3,2, Robert Zeiser4,2, Debra K. Czerwinski2, Robert S. Negrin2,5, Ronald Levy2,5
1Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA
2Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
3Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
4Department of Hematology and Oncology, Albert-Ludwigs University Freiburg, Freiburg, Germany
5R. Levy and R. S. Negrin are co-senior authors.

Tóm tắt

AbstractThere 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) B 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 B 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. © 2008 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1084/jem.20051511

10.1084/jem.20050463

10.1158/0008-5472.CAN-04-4043

10.1038/nm1093

Woo EY, 2001, Regulatory CD4+CD25+ T cells in tumors from patients with early‐stage non‐small cell lung cancer and late‐stage ovarian cancer, Cancer Res, 61, 4766

10.4049/jimmunol.169.5.2756

10.1182/blood-2005-08-3376

10.1038/nm0904-900

10.1182/blood-2005-09-3671

10.1038/nrc1586

10.4049/jimmunol.178.7.4051

10.1158/0008-5472.CAN-06-1822

10.4049/jimmunol.173.2.1444

10.4049/jimmunol.163.10.5211

Steitz J, 2001, Depletion of CD25+ CD4+ T cells and treatment with tyrosinase‐related protein 2‐transduced dendritic cells enhance the interferon {alpha}‐induced. CD8+ T‐cell‐dependent immune defense of B16 melanoma, Cancer Res, 61, 8643

10.1172/JCI25947

10.1084/jem.20050940

10.1084/jem.20041684

10.1002/1521-4141(200211)32:11<3267::AID-IMMU3267>3.0.CO;2-1

10.1182/blood.V99.9.3326

Gray CP, 2003, Association of increased levels of heavy‐chain ferritin with increased CD4+ CD25+ regulatory T‐cell levels in patients with melanoma, Clin Cancer Res, 9, 2551

10.1158/0008-5472.CAN-05-0141

10.1172/JCI19441

10.4049/jimmunol.173.7.4433

10.1084/jem.20061660

10.1182/blood-2007-03-082578

10.1182/blood-2007-08-105395

10.1158/0008-5472.CAN-06-0261

10.4049/jimmunol.177.2.840

10.1002/eji.200636435

10.1073/pnas.0509484103

10.1038/nm1201-1339

10.1182/blood-2005-04-1565

10.1056/NEJMoa041869

10.1182/blood-2004-06-2298

10.1200/JCO.2006.06.1648

10.1182/blood-2006-11-058040

10.1182/blood-2007-06-094482

10.1002/1521-4141(200205)32:5<1403::AID-IMMU1403>3.0.CO;2-Y

10.1182/blood.V98.3.533

10.1128/JVI.78.4.1665-1674.2004

Farina P, 2007, The architectural pattern of FoxP3+ T cells predicts risk of transformation in patients with follicular lymphoma, Am Soc Hematol Annu Meet, 110, 112a

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Thông tin xuất bản

International Journal of Cancer

Tập 124 Số 1

239-244

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