Cancer Immunology, Immunotherapy

, Volume 67, Issue 7, pp 1113–1121 | Cite as

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

  • Lawrence F. Kuklinski
  • Shaofeng Yan
  • Zhongze Li
  • Jan L. Fisher
  • Chao Cheng
  • Randolph J. Noelle
  • Christina V. Angeles
  • Mary Jo Turk
  • Marc S. Ernstoff
Original Article


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.


VISTA Melanoma Survival Checkpoint inhibitor Tumor microenvironment Tumor-infiltrating lymphocytes 



American Joint Committee on Cancer


Confidence interval


Hazard ratio


The cancer genome atlas


Tumor-infiltrating inflammatory cells


Author contributions

LFK: interpreted data and wrote the manuscript. SY: conceived the study, interpreted data, and wrote the manuscript. ZL: analyzed data. JLF: interpreted data and wrote the manuscript. CC: analyzed data. RJN: edited the manuscript. CVA: edited the manuscript. MJT: edited the manuscript. MSE: conceived and supervised the study, interpreted data, and wrote the manuscript.


This work was supported by National Cancer Institute Grant NCI P30CA023108, Dartmouth Hitchcock Melanoma Funds, and funding provided by Immunext. In addition, Dr. Randolph Noelle has support from NCI RO1 AI098007 and NCI RO1 CA214062, Dr. Mary Jo Turk from NCI RO1 CA214062, and Dr. Marc Ernstoff from NCI PO1 CA206980 and NCI P30 CA016056.

Compliance with ethical standards

Conflict of interest

Randolph J. Noelle is the co-founder of ImmuNext. All other authors declare no conflicts of interest.

Ethical approval

This study was approved by the Dartmouth College Committee for the Protection of Human Subjects/Institutional Review Board, approval number 23388, and was in compliance with ethical guidelines according to the Declaration of Helsinki.

Informed consent

Informed consent was waived by the Institutional Review Board on the grounds of being a retrospective study using tumor tissue already archived by the Dartmouth-Hitchcock Medical Center Department of Pathology tumor bank. Many patients were deceased. All data was abstracted from the medical record and had previously been obtained for the purposes of medical care.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lawrence F. Kuklinski
    • 1
    • 2
  • Shaofeng Yan
    • 3
  • Zhongze Li
    • 4
  • Jan L. Fisher
    • 5
  • Chao Cheng
    • 6
  • Randolph J. Noelle
    • 7
  • Christina V. Angeles
    • 8
  • Mary Jo Turk
    • 7
  • Marc S. Ernstoff
    • 9
  1. 1.Geisel School of Medicine at DartmouthHanoverUSA
  2. 2.Department of MedicineSanta Barbara Cottage HospitalSanta BarbaraUSA
  3. 3.Department of Pathology and Laboratory MedicineDartmouth-Hitchcock Medical Center, Geisel School of Medicine at DartmouthLebanonUSA
  4. 4.Biostatistics Shared Resource, Norris Cotton Cancer CenterDartmouth-Hitchock Medical CenterLebanonUSA
  5. 5.Department of Medicine, Norris Cotton Cancer CenterGeisel School of Medicine at DartmouthLebanonUSA
  6. 6.Departments of Biomedical Data Sciences, Molecular and Systems Biology, Norris Cotton Cancer CenterGeisel School of Medicine at DartmouthLebanonUSA
  7. 7.Department of Microbiology and Immunology, Norris Cotton Cancer CenterGeisel School of Medicine at DartmouthHanoverUSA
  8. 8.Department of Surgery, Norris Cotton Cancer CenterDartmouth-Hitchcock Medical CenterLebanonUSA
  9. 9.Roswell Park Cancer InstituteUniversity of Buffalo, The State University of New YorkBuffaloUSA

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