Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
Harvard University · Dana-Farber Cancer Institute · +3 more institutions
Abstract
Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+))…
Citation impact
- FWCI
- 37.04
- Percentile
- 100%
- References
- 78
Authors
4- JDJaikumar Duraiswamy
Harvard University, Dana-Farber Cancer Institute, Cancer Research Center, Center for Cancer Research, University of Pennsylvania
- KMKaren M. Kaluza
Harvard University, Dana-Farber Cancer Institute, Cancer Research Center, Center for Cancer Research, University of Pennsylvania
- GJGordon J. Freeman
Harvard University, Dana-Farber Cancer Institute, Cancer Research Center, Center for Cancer Research, University of Pennsylvania
- GCGeorge CoukosCorresponding
Harvard University, Dana-Farber Cancer Institute, Cancer Research Center, Center for Cancer Research, University of Pennsylvania
Topics & keywords
- Blockade
- CTLA-4
- Cancer research
- Dual (grammatical number)
- Medicine
- Function (biology)
- Dual function
- T cell
- Good health and well-being