Vascular endothelial growth factor suppresses dendritic cells function of human prostate cancer
OncoTargets and Therapy
Vascular endothelial growth factor suppresses dendritic cells function of human prostate cancer
0 Wen-kun Bai Wei Zhang Bing hu
8 1 0 2 - l u J - 2 1 n o 7 0 2 . 6 4 . 9 5 . 7 3 y b / m o c . s s re . .vdoep lsyeon w u /ww lan /: o tsp rse th rp PowerdbyTCPDF(ww.tcpdf.org) O r i g i n a l r e s e a r c h Purpose: Prostate cancer (PCa) patients often have dendritic cell (DC) function defects, but the mechanism is not clear. The aim of this study was to detect the effect of vascular endothelial growth factor (VEGF) in mature DCs. Patients and methods: In this study, we chose 30 PCa patients, 10 prostatic intraepithelial neoplasia (PIN) patients and 30 benign prostatic hyperplasia (BPH) patients, and compared the composition of peripheral blood T cells, the composition and function of local dendritic cells in prostate tissue, and the density of local VEGF. Results: The results showed that the numbers of total DCs, mature and functional DCs, and CD4+ T cells were inhibited in PCa, and the inhibitory effect was enhanced with increased malignancy. In addition, the infiltration density of VEGF-positive cells was increased in PCa, and this increase was associated with an increased malignant degree of PCa. The inhibition of tumor immunity in patients with PCa is achieved by inhibiting the function of dendritic cells. Conclusion: VEGF plays an important role in the inhibition of the maturation and function of dendritic cells, and this inhibition is gradually increased with an increasing malignant degree of PCa.
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Department of Ultrasound in
Medicine, shanghai Jiao Tong
University a ffiliated 6th People’s
hospital, shanghai institute
of Ultrasound in Medicine,
shanghai, china
Early theories did not consider the prostate to be an
organ monitored by the body’s immune system,5 but nearly
7 years of research has overthrown this viewpoint, suggesting
that the treatment of PCa may potentially work by
activating the immune system.6 Therefore, increasing attention to
the clinical treatment of PCa, especially in late
androgenindependent or distant metastasis, focuses on activating
the human immune system to treat PCa. Sipuleucel-T was
2108 approved by the United States Food and Drug Administration
l--Ju for PCa therapy in 2010.7
12 Previous studies have demonstrated that the quantity and
7no activity of DCs in PCa patients are significantly lower than
.602 in healthy controls,8 and in vitro experiments verified that
.459 PCa cells induce apoptosis, as well as suppress the
regenera.73 tion and differentiation of DCs.9 Studies also showed that
/yb the numbers of DCs are reduced in PCa tissues compared
.com to prostatic hyperplasia (BPH) tissues, and the levels of
s
re . infiltrating DCs are further decreased with the advancement
s
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/ww lan disease, and the immunosuppressive tumor
microenviron/: o
tsp rse ment may limit their effectiveness.11 Therefore, it is
necestrohm ropF sary to determine the mechanism of immune inhibition to
fd overcome the immune restriction and improve the efficacy
aed of immunotherapy.
lonw Vascular endothelial growth factor (VEGF), which
ydo induces neoangiogenesis and the blockade of angiogenesis,
reap plays an important role in the development and metastasis
hT of solid tumors, and targeting VEGF has become a useful
nad approach in cancer therapy.12 The inhibition of VEGF in
trseg a mouse model leads to increased antigen uptake and the
oaT migration of tumor-associated DCs.13 In the human tongue
cnO carcinoma, cancer cells could be inhibited in proliferation and
be increased in apoptosis by knocking down the expression
of VEGF, and maturation of DCs also could be improved.14
VEGF also influences the effect of DCs on therapy in the
model of colon cancer-induced malignant ascites.15 VEGF
expression in the peripheral blood and neoplasm nest from
patients with oral squamous cell carcinoma (OSCC) was
positively correlated with the course of the disease, while an
inverse correlation between VEGF expression and DCs was
identified in the peripheral blood.14 Some clinical research
has been carried out that blocks VEGF to improve the
antitumor responses in treating PCa patients.16 PCa is divided into
three categories, which fit the following standard definitions:
low-risk PCa (biopsy Gleason grade 7 or prostate-specific
antigen (PSA) 10 ng/mL), intermediate-risk PCa (biopsy
Gleason score 7 or PSA 10–20 ng/mL), and high-risk PCa
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(biopsy Gleason score 7 or PSA 20 ng/mL).17–20
Determining the status of DC and VEGF expression in different
degrees of PCa patients is needed.
In this study, we compared the composition and functional
status of DCs in prostate tissues of patients with BPH,
prostatic intraepithelial neoplasia (PIN) and PCa and compared
the expression of VEGF in these prostate tissues. We also
compared (...truncated)