B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders.
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.
Wilcox
Ryan A
RA
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Feldman
Andrew L
AL
Wada
David A
DA
Yang
Zhi-Zhang
ZZ
Comfere
Nneka I
NI
Dong
Haidong
H
Kwon
Eugene D
ED
Novak
Anne J
AJ
Markovic
Svetomir N
SN
Pittelkow
Mark R
MR
Witzig
Thomas E
TE
Ansell
Stephen M
SM
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors