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Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression. Cancer Immunol Res 2019 09;7(9):1497-1510



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Pubmed Central ID




Scopus ID

2-s2.0-85071783703   5 Citations


Immune-checkpoint protein V-domain immunoglobulin suppressor of T-cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. This study identified a role of VISTA in regulating Toll-like receptor (TLR) signaling in myeloid cells and controlling myeloid cell-mediated inflammation and immunosuppression. VISTA modulated the polyubiquitination and protein expression of TRAF6. Consequently, VISTA dampened TLR-mediated activation of MAPK/AP-1 and IKK/NF-κB signaling cascades. At cellular levels, VISTA regulated the effector functions of myeloid-derived suppressor cells and tolerogenic dendritic cell (DC) subsets. Blocking VISTA augmented their ability to produce proinflammatory mediators and diminished their T cell-suppressive functions. These myeloid cell-dependent effects resulted in a stimulatory tumor microenvironment that promoted T-cell infiltration and activation. We conclude that VISTA is a critical myeloid cell-intrinsic immune-checkpoint protein and that the reprogramming of tolerogenic myeloid cells following VISTA blockade promotes the development of T cell-mediated antitumor immunity.

Author List

Xu W, Dong J, Zheng Y, Zhou J, Yuan Y, Ta HM, Miller HE, Olson M, Rajasekaran K, Ernstoff MS, Wang D, Malarkannan S, Wang L


Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5