Keehoon JUNG
Department of Anatomy and Cell Biology/Biomedical Sciences, Seoul
National University College of Medicine, Korea

Real-time intravital characterization of non-classicalmonocytes in cancers
Keehoon JUNG

Contact : keehoon.jung [at sign] snu.ac.kr
Please replace [at sign] with @.

Research Interests
Cancer Immunology, In Vivo Imaging, Single-Cell Genomics, Vascular Biology, Drug Development

Department of Anatomy and Cell Biology/Biomedical Sciences
Seoul National University College of Medicine, Korea

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. However, current anti-VEGF therapies
for CRC provide limited survival benefit as tumors rapidly develop resistance to these agents.
We have developed a miniaturized confocal endomicroscopy technique for spontaneous CRC models in mice. We
recently also established a novel abdominal imaging window. These unique systems enable us to monitor the CRC and
its immune microenvironment longitudinally with a video-rate intravital multi-photon microscope. Using these in vivo
imaging methods and CRC models, we have uncovered an immunosuppressive role for non-classical Ly6Clow

Education20052010

monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated
B.S. in Biological Sciences, KAIST, Korea
Ph.D. in Biological Sciences and Biomedical Science & Engineering Program, KAIST, Korea

in both human and murine tumors following the 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 inendothelial cells. Intravital microscopy revealed that CX3CR1 is critical for Ly6Clow monocyte transmigration across theendothelium in tumors. Moreover, Ly6Clow monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which

Professional Career2010 -20132013 -2018
2018- present

Research Fellow at Wellman Center (In Vivo Imaging), Harvard Medical School / MGH
Research Fellow at Steele Laboratories for Tumor Biology, Harvard Medical School / MGH
Assistant Professor, Seoul National University

inhibits adaptive immunity. Preventing Ly6Clow monocyte or Ly6G+ neutrophil
infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2
therapy. Further more, 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
revealed molecular mechanisms underlying anti-angiogenic treatment resistance,suggesting potential immunomodulatory strategies to enhance the long-term

Honors20182018 -2027
2017
2016
2016

clinical outcome of anti-VEGF therapies, proven by state-of-the-art in vivo imaging
Milstein Award, International Cytokine & Interferon Society (ICIS)

Fig. 1. Non-classical monocytes flow
through blood vessels as they infiltratetumors.

Creative- Pioneering Researchers Program, Seoul National University
Speaker Award, Gordon Research Conference - Angiogenesis
Bristol-Myers Squibb (BMS) Award, Tumor Immunology and Immunotherapy Meeting
AACR-GYRIG Scholar-in-Training Award, AACR Annual Meeting

Publications
1. Choo YW, Jeong J, Jung K. Recent advances in intravital microscopy for investigation of dynamic cellular behavior in vivo. BMB Reports, (2020).
2.

modalities.

Jeong J, Suh Y, Jung K. Context drives diversification of monocytes and neutrophils in orchestrating the tumor microenvironment. Frontiers inImmunology (2019).
Jung K. et al., Targeting CXCR4-dependent immunosuppressive Ly6C(low) monocytes improves antiangiogenic therapy in colorectal cancer.

3. Proc Natl Acad Sci USA (2017).

4. Jung K. et al., Ly6C(lo) monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy. J Clin Invest (2017).

References[ 1 ] Choo YW, Jeong J, Jung K. Recent advances in intravital microscopy for investigation of dynamic cellular behavior
in vivo. BMB Reports, (2020).
[ 2 ] Jeong J, Suh Y, Jung K. Context drives diversification of monocytes and neutrophils in orchestrating the tumor
microenvironment. Frontiers in Immunology (2019).
[ 3 ] Jung K. et al., Targeting CXCR4-dependent immunosuppressive Ly6C(low) monocytes improves antiangiogenic
therapy in colorectal cancer. Proc Natl Acad Sci USA (2017).
[ 4 ] Jung K. et al., Ly6C(lo) monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy.
J Clin Invest (2017).
[ 5 ] Jung K. et al., Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res (2013).

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