동물분자생체공학연구소 주관 초청강연 48
연사 : 정기훈 교수 (서울대학교 의과대학)
제목 : Myeloid cells in cancer immunity: Real-time intravital investigation at single-cell level
일시 : 2019년 12월 18일 수요일 오후 4시
장소 : 생명과학관 서관 101호
초록
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. Using these in vivo imaging methods and CRC models, 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 the VEGF signaling blockade, resulting in recruitment of CX3CR1+ Ly6Clow monocytes into the tumor. Intravital microscopy revealed thatCX3CR1 is critical for Ly6Clow monocyte transmigration across theendothelium in tumors. Preventing Ly6Clow monocyte or Ly6G+ neutrophilinfiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2therapy.
Taken together, we identified immunosuppressivenon-classical Ly6Clow monocytes as key players in tumor resistance toanti-angiogenic therapy in CRCs. We also revealed molecular mechanismsunderlying anti-angiogenic treatment resistance, suggesting potentialimmunomodulatory strategies to enhance the long-term clinical outcome of anti-VEGFtherapies, proven by state-of-the-art in vivo imaging modalities.