Researchers at the Geisel School of Medicine at Dartmouth have found that the body's immune system response was enhanced when they disrupted VISTA, a protein that prevents the immune system from overreacting. Understanding how checkpoint regulators like VISTA function is important to cancer researchers, who hope to use the immune system to attack tumors. The study, "VISTA deficiency synergizes with a nonredundant immune checkpoint pathway and leads to enhanced immune activation," was presented at the American Association for Cancer Research Annual Meeting in San Diego, CA.
"Because there are multiple immune suppressive pathways, disrupting a single pathway like VISTA might not have led us to obvious alterations in the immune response," said Li Wang, PhD, assistant professor of Microbiology and Immunology at Geisel. "Our data showed clear chronic inflammation due to VISTA deficiency, which leads us to conclude that VISTA likely plays an important role in regulating immunity."
Wang and her colleagues hope to build on these findings to define the molecular pathway involved in VISTA-mediated immune regulation.
This work is supported by NIH grant CA164225 (L.W.), Melanoma Research Foundation Career Development Award (L.W.), Hitchcock Foundation Research grant (L.W.), AI048667 (R.J.N), Wellcome Trust (R.J.N) and the Medical Research Council Centre for Transplantation and Biomedical Research Center at King's College London (RJN). Conflicts of interest: The authors RJN and LW are involved with ImmuNext Inc. and receive financial support for the development of anti-VISTA for immunotherapy.