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Seminar

2/1 (Fri) 14:00 Special Seminar
Name : 관리자 | Date : 2019.01.24 16:48 | Views : 892

Title: Real-time intravital characterization of the immune microenvironment in cancers


Speaker: Keehoon Jung, Ph.D., Seoul National University College of Medicine (Host : Jaewon Ko)


Time: 14:00, February 1 (Fri), 2019
        

Venue: Room 506, Building E4, DGIST


Abstract : Colorectal cancer (CRC) is the leading cause of cancer-related death
worldwide. However, current anti-VEGF therapies for CRC provide limited survival
benefit as tumors rapidly develop resistance to these agents.
We have recently established a novel abdominal imaging window for CRC
models in mice. This unique system enables us to monitor the CRC and its immune
microenvironment longitudinally with a video-rate intravital multi-photon
microscope. Using these CRC models and in vivo imaging methods, we have
uncovered an immunosuppressive role for non-classical Ly6Clow monocytes that
mediates resistance to anti-VEGFR2 treatment. We found that the chemokine
CX3CL1 was upregulated in both human and murine tumors following VEGF
signaling blockade, resulting in recruitment of CX3CR1+ Ly6Clow monocytes into
the tumor. We also found that treatment with VEGF-A reduced expression of
CX3CL1 in endothelial cells. Intravital microscopy revealed that CX3CR1 is critical
for Ly6Clow monocyte transmigration across the endothelium in tumors. Moreover,
Ly6Clow monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which
inhibits adaptive immunity. Preventing Ly6Clow monocyte or Ly6G+ neutrophil
infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2
therapy. Furthermore, we developed a gene therapy using a nanoparticle
formulated with a siRNA against CX3CL1, which reduced Ly6Clow monocyte
recruitment and improved outcome of anti-VEGFR2 therapy in mouse CRCs.
Taken together, we identified immunosuppressive non-classical Ly6Clow
monocytes as key players in tumor resistance to anti-angiogenic therapy in CRCs.
We also reveal molecular mechanisms underlying anti-angiogenic treatment
resistance, suggesting potential immunomodulatory strategies to enhance the
long-term clinical outcome of anti-VEGF therapies, proven by state-of-the-art in
vivo imaging modalities.

Person in charge : Sora Lee


Contact: srlee@dgist.ac.kr, 053)785-6102

IP : 10.140.1.*** share
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No File Subject Name Date Views
png 관리자 2019.02.19 4,247
125 pdf 관리자 2019.01.25 2,510
124 pdf 관리자 2019.01.24 963
pdf 관리자 2019.01.24 893
122 pdf 관리자 2019.01.24 896
121 pdf 관리자 2018.12.06 1,077
120 pdf 관리자 2018.11.20 1,034
119 pdf 관리자 2018.11.15 1,105
118 pdf 관리자 2018.11.15 1,097
117 pdf 관리자 2018.10.15 1,266
116 pdf 관리자 2018.10.11 1,231
115 pdf 관리자 2018.10.11 1,487
114 pdf 관리자 2018.10.10 1,530
113 pdf 관리자 2018.10.02 1,580
112 pdf 관리자 2018.09.10 1,690
111 pdf 관리자 2018.09.10 1,601
110 pdf 관리자 2018.08.29 1,774
109 jpg 관리자 2018.08.20 5,787
108 pdf 관리자 2018.07.26 5,321
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106 pdf 관리자 2018.06.21 6,128