Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression.

Autor:	Xu W; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin., Dong J; Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, Ohio., Zheng Y; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin.; Blood Research Institute, Milwaukee, Wisconsin., Zhou J; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin.; Department of Immunology, Children's Hospital of Chongqing Medical University, Yuzhong District, Chongqing, P.R. China., Yuan Y; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin., Ta HM; Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, Ohio., Miller HE; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin., Olson M; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin., Rajasekaran K; Blood Research Institute, Milwaukee, Wisconsin., Ernstoff MS; Roswell Park Cancer Institute, Buffalo, New York., Wang D; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin.; Blood Research Institute, Milwaukee, Wisconsin., Malarkannan S; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin.; Blood Research Institute, Milwaukee, Wisconsin.; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin., Wang L; Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, Ohio. wangl9@ccf.org.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2019 Sep; Vol. 7 (9), pp. 1497-1510. Date of Electronic Publication: 2019 Jul 24.
DOI:	10.1158/2326-6066.CIR-18-0489
Abstrakt:	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. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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