한빛사 논문
Seungman Parka,h,i, Yu Shib, Byoung Choul Kimc,d,e,f, Myung Hyun Joc, Leilani O. Cruzg, Zheming Goua, Taekjip Hac,d,e, Li-Fan Lug, Daniel H. Reichb, Yun Chena,h,i,*
aDepartment of Mechanical Engineering, Johns Hopkins University, MD, 21218, USA
bDepartment of Physics & Astronomy, Johns Hopkins University, MD, 21218, USA
cDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
dDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
eHoward Hughes Medical Institute, Baltimore, MD, 21205, USA
fDivision of Nano-Bioengineering, Incheon National University, Incheon, 22012, South Korea
gDivision of Biological Science, University of California, San Diego, CA, 92093, USA
hCenter for Cell Dynamics, Johns Hopkins University, MD, 21218, USA
iInstitute for NanoBioTechnology, Johns Hopkins University, MD, 21218, USA
*Corresponding author
Abstract
In this study, we investigated the biophysical interaction between cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and CD80. CTLA-4 is a key molecule in immunosuppression, and CD80 is a costimulatory receptor promoting T cell activation. We observed that after cell-cell contact was established between breast cancer cells and antigen presenting cells (APCs), CTLA-4 expressed on the breast cancer cells bind to CD80 expressed on the APCs, and underwent trans-endocytosis to deplete CD80. Force measurement and live cell imaging revealed that upon binding to CD80, forces generated by breast cancer cells and transmitted via CTLA-4 were sufficiently strong to displace CD80 from the surface of APCs to be internalized by breast cancer cells. We further demonstrated that because of the force-dependent trans-endocytosis of CD80, the capacity of APCs to activate T cells was significantly attenuated. Furthermore, inhibiting force generation in cancer cells would increase the T cell activating capacity of APCs. Our results provide a possible mechanism behind the immunosuppression commonly seen in breast cancer patients, and may lead to a new strategy to restore anti-tumor immunity by inhibiting pathways of force-generation.
논문정보
관련 링크