Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.
Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface. B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.
Curiel
Tyler J
TJ
Tulane University Health Science Center, New Orleans, Louisiana, USA.
Wei
Shuang
S
Dong
Haidong
H
Alvarez
Xavier
X
Cheng
Pui
P
Mottram
Peter
P
Krzysiek
Roman
R
Knutson
Keith L
KL
Daniel
Ben
B
Zimmermann
Maria Carla
MC
David
Odile
O
Burow
Matthew
M
Gordon
Alan
A
Dhurandhar
Nina
N
Myers
Leann
L
Berggren
Ruth
R
Hemminki
Akseli
A
Alvarez
Ronald D
RD
Emilie
Dominique
D
Curiel
David T
DT
Chen
Lieping
L
Zou
Weiping
W
D000818:Animals; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D022423:Myeloid Cells / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D016753:Interleukin-10; D018664:Interleukin-12