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PMID: 19597183 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders.

Blood ·Vol. 114 ·No. 10 ·2009-09-03 ·Pages 2149-58

Wilcox RA, Feldman AL, Wada DA, Yang ZZ, Comfere NI, Dong H, Kwon ED, Novak AJ, Markovic SN, Pittelkow MR, Witzig TE, Ansell SM

Abstract

Stromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell-derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell-derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/co-inhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3(+) regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach.

MeSH Terms
Antigens, CD/biosynthesis,immunology B7-H1 Antigen Cell Line, Tumor Cell Proliferation Forkhead Transcription Factors Gene Expression Regulation, Neoplastic/immunology Humans Immune Tolerance Lymphoproliferative Disorders/immunology,metabolism,therapy Monocytes/immunology,metabolism T-Lymphocytes, Regulatory/immunology,metabolism
Chemicals
Antigens, CD B7-H1 Antigen CD274 protein, human FOXP3 protein, human Forkhead Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Wilcox Ryan A
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Feldman Andrew L
Wada David A
Yang Zhi-Zhang
Comfere Nneka I
Dong Haidong
Kwon Eugene D
Novak Anne J
Markovic Svetomir N
Pittelkow Mark R
Witzig Thomas E
Ansell Stephen M
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2009-04-216671
Published
2009-09-03
Epub
2009-00-13
Pages
2149-58
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2744574
Subset
IM
Grants
NCI NIH HHS · P50 CA097274 · United States
NCI NIH HHS · R01 CA092104 · United States
NCI NIH HHS · CA92104 · United States
NCI NIH HHS · CA97274 · United States
External Links
PubMed source DOI: 10.1182/blood-2009-04-216671 PMC Full Text View journal details
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