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      VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival.

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          Abstract

          Adaptive immune responses contribute to the pathogenesis of melanoma by facilitating immune evasion. V-domain Ig suppressor of T-cell activation (VISTA) is a potent negative regulator of T-cell function and is expressed at high levels on monocytes, granulocytes, and macrophages, and at lower densities on T-cell populations within the tumor microenvironment. In this study, 85 primary melanoma specimens were selected from pathology tissue archives and immunohistochemically stained for CD3, PD-1, PD-L1, and VISTA. Pearson's correlation coefficients identified associations in expression between VISTA and myeloid infiltrate (r = 0.28, p = 0.009) and the density of PD-1+ inflammatory cells (r = 0.31, p = 0.005). The presence of VISTA was associated with a significantly worse disease-specific survival in univariate analysis (hazard ratio = 3.57, p = 0.005) and multivariate analysis (hazard ratio = 3.02, p = 0.02). Our findings show that VISTA expression is an independent negative prognostic factor in primary cutaneous melanoma and suggests its potential as an adjuvant immunotherapeutic intervention in the future.

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          Author and article information

          Journal
          Cancer Immunol. Immunother.
          Cancer immunology, immunotherapy : CII
          Springer Nature America, Inc
          1432-0851
          0340-7004
          Jul 2018
          : 67
          : 7
          Affiliations
          [1 ] Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
          [2 ] Department of Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA, USA.
          [3 ] Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
          [4 ] Biostatistics Shared Resource, Norris Cotton Cancer Center, Dartmouth-Hitchock Medical Center, Lebanon, NH, USA.
          [5 ] Department of Medicine, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
          [6 ] Departments of Biomedical Data Sciences, Molecular and Systems Biology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, USA.
          [7 ] Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
          [8 ] Department of Surgery, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
          [9 ] Roswell Park Cancer Institute, University of Buffalo, The State University of New York, Elm and Carlton, Buffalo, NY, 14263, USA. marc.ernstoff@roswellpark.org.
          Article
          10.1007/s00262-018-2169-1
          10.1007/s00262-018-2169-1
          29737375
          60afdf59-f84f-49b6-a1c9-09c63b0441c1
          History

          Melanoma,VISTA,Tumor-infiltrating lymphocytes,Tumor microenvironment,Survival,Checkpoint inhibitor

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