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

被引:91
作者
Kuklinski, Lawrence F. [1 ,2 ]
Yan, Shaofeng [3 ]
Li, Zhongze [4 ]
Fisher, Jan L. [5 ]
Cheng, Chao [6 ,7 ,8 ]
Noelle, Randolph J. [9 ]
Angeles, Christina V. [10 ]
Turk, Mary Jo [9 ]
Ernstoff, Marc S. [11 ]
机构
[1] Geisel Sch Med Dartmouth, Hanover, NH USA
[2] Santa Barbara Cottage Hosp, Dept Med, Santa Barbara, CA USA
[3] Geisel Sch Med Dartmouth, Dartmouth Hitchcock Med Ctr, Dept Pathol & Lab Med, Lebanon, NH USA
[4] Dartmouth Hitchock Med Ctr, Norris Cotton Canc Ctr, Biostat Shared Resource, Lebanon, NH USA
[5] Geisel Sch Med Dartmouth, Dept Med, Norris Cotton Canc Ctr, Lebanon, NH USA
[6] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Biomed Data Sci, Lebanon, NH USA
[7] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Mol, Lebanon, NH USA
[8] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Syst Biol, Lebanon, NH USA
[9] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Microbiol & Immunol, Hanover, NH USA
[10] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Surg, Lebanon, NH 03766 USA
[11] SUNY Buffalo, Roswell Pk Canc Inst, Buffalo, NY 14263 USA
关键词
VISTA; Melanoma; Survival; Checkpoint inhibitor; Tumor microenvironment; Tumor-infiltrating lymphocytes; VERTICAL GROWTH-PHASE; T-CELLS; CANCER-IMMUNOTHERAPY; MALIGNANT-MELANOMA; STAGE-III; LIGAND; PD-1; PROGNOSIS; BLOCKADE; THERAPY;
D O I
10.1007/s00262-018-2169-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1113 / 1121
页数:9
相关论文
共 35 条
  • [1] Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired
    Ahmadzadeh, Mojgan
    Johnson, Laura A.
    Heemskerk, Bianca
    Wunderlich, John R.
    Dudley, Mark E.
    White, Donald E.
    Rosenberg, Steven A.
    [J]. BLOOD, 2009, 114 (08) : 1537 - 1544
  • [2] Genomic Classification of Cutaneous Melanoma
    Akbani, Rehan
    Akdemir, Kadir C.
    Aksoy, B. Arman
    Albert, Monique
    Ally, Adrian
    Amin, Samirkumar B.
    Arachchi, Harindra
    Arora, Arshi
    Auman, J. Todd
    Ayala, Brenda
    Baboud, Julien
    Balasundaram, Miruna
    Balu, Saianand
    Barnabas, Nandita
    Bartlett, John
    Bartlett, Pam
    Bastian, Boris C.
    Baylin, Stephen B.
    Behera, Madhusmita
    Belyaev, Dmitry
    Benz, Christopher
    Bernard, Brady
    Beroukhim, Rameen
    Bir, Natalie
    Black, Aaron D.
    Bodenheimer, Tom
    Boice, Lori
    Boland, Genevieve M.
    Bono, Riccardo
    Bootwalla, Moiz S.
    Bosenberg, Marcus
    Bowen, Jay
    Bowlby, Reanne
    Bristow, Christopher A.
    Brockway-Lunardi, Laura
    Brooks, Denise
    Brzezinski, Jakub
    Bshara, Wiam
    Buda, Elizabeth
    Burns, William R.
    Butterfield, Yaron S. N.
    Button, Michael
    Calderone, Tiffany
    Cappellini, Giancarlo Antonini
    Carter, Candace
    Carter, Scott L.
    Cherney, Lynn
    Cherniack, Andrew D.
    Chevalier, Aaron
    Chin, Lynda
    [J]. CELL, 2015, 161 (07) : 1681 - 1696
  • [3] Tumor-Infiltrating Lymphocyte Grade Is an Independent Predictor of Sentinel Lymph Node Status and Survival in Patients With Cutaneous Melanoma
    Azimi, Farhad
    Scolyer, Richard A.
    Rumcheva, Pavlina
    Moncrieff, Marc
    Murali, Rajmohan
    McCarthy, Stanley W.
    Saw, Robyn P.
    Thompson, John F.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (21) : 2678 - 2683
  • [4] Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system
    Balch, CM
    Soong, SJ
    Gershenwald, JE
    Thompson, JF
    Reintgen, DS
    Cascinelli, N
    Urist, M
    McMasters, KM
    Ross, MI
    Kirkwood, JM
    Atkins, MB
    Thompson, JA
    Coit, DG
    Byrd, D
    Desmond, R
    Zhang, YT
    Liu, PY
    Lyman, GH
    Morabito, A
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) : 3622 - 3634
  • [5] CLARK WH, 1969, CANCER RES, V29, P705
  • [6] Clemente CG, 1996, CANCER, V77, P1303, DOI 10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO
  • [7] 2-5
  • [8] Association of PD-1/PD-L axis expression with cytolytic activity, mutational load, and prognosis in melanoma and other solid tumors
    Danilova, Ludmila
    Wang, Hao
    Sunshine, Joel
    Kaunitz, Genevieve J.
    Cottrell, Tricia R.
    Xu, Haiying
    Esandrio, Jessica
    Anders, Robert A.
    Cope, Leslie
    Pardoll, Drew M.
    Drake, Charles G.
    Taube, Janis M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (48) : E7769 - E7777
  • [9] Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
    Eggermont, A. M. M.
    Chiarion-Sileni, V.
    Grob, J. -J.
    Dummer, R.
    Wolchok, J. D.
    Schmidt, H.
    Hamid, O.
    Robert, C.
    Ascierto, P. A.
    Richards, J. M.
    Lebbe, C.
    Ferraresi, V.
    Smylie, M.
    Weber, J. S.
    Maio, M.
    Bastholt, L.
    Mortier, L.
    Thomas, L.
    Tahir, S.
    Hauschild, A.
    Hassel, J. C.
    Hodi, F. S.
    Taitt, C.
    de Pril, V.
    de Schaetzen, G.
    Suciu, S.
    Testori, A.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (19) : 1845 - 1855
  • [10] Cutting Edge: A Monoclonal Antibody Specific for the Programmed Death-1 Homolog Prevents Graft-versus-Host Disease in Mouse Models
    Flies, Dallas B.
    Wang, Shengdian
    Xu, Haiying
    Chen, Lieping
    [J]. JOURNAL OF IMMUNOLOGY, 2011, 187 (04) : 1537 - 1541