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

被引:92
|
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
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