4.7 Article

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

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 67, Issue 7, Pages 1113-1121

Publisher

SPRINGER
DOI: 10.1007/s00262-018-2169-1

Keywords

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

Funding

  1. National Cancer Institute Grant [NCI P30CA023108]
  2. Dartmouth Hitchcock Melanoma Funds
  3. Immunext
  4. NCI [RO1 AI098007, RO1 CA214062, PO1 CA206980, P30 CA016056]

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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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