Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses
Abstract
Multiple immune-checkpoint proteins, such as programmed death 1 (PD-1), LAG3, and TIM3, are coexpressed on immune cells and functionally synergize with each other. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a recently identified immune-checkpoint molecule that suppresses T-cell activation. This study establishes that VISTA and PD-1 exert nonredundant immune regulatory functions and synergistically regulate T-cell responses. Combinatorial treatment using VISTA- and PD-ligand 1-specific monoclonal antibodies achieved synergistic therapeutic efficacy in murine tumor models. This study critically advances our knowledge of the immune regulatory function of VISTA and provides a rationale for targeting both VISTA and PD-1 to more effectively treat T-cell-regulated diseases such as cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 11, 2015
- Source ID
- 10.1073/pnas.1420370112
Entities
People
- Arief A. Suriawinata
- Austin D. Schenk
- Halli E. Miller
- Indira Guleria
- Juan Putra
- Jun Liu
- Li Wang
- Richard J. Barth
- Wenna Chen
- Yina H Huang
- Ying Yuan
Organizations
- China Pharmaceutical University
- Geisel School of Medicine
- Harvard Medical School
- Medical College of Wisconsin
- National Cancer Institute
- United States Department of Defense