Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade

被引：316

作者：

da Silva, Ines Pires ^{[1
,2
,3
,6
,7
]}

Gallois, Anne ^{[4
]}

Jimenez-Baranda, Sonia ^{[1
]}

Khan, Shaukat ^{[1
]}

Anderson, Ana C. ^{[5
]}

Kuchroo, Vijay K. ^{[5
]}

Osman, Iman ^{[1
,2
,3
]}

Bhardwaj, Nina ^{[3
,4
]}

机构：

[1] NYU Med Ctr, Inst Canc, New York, NY 10016 USA

[2] NYU Med Ctr, Ronald Perelman Dept Dermatol, New York, NY 10016 USA

[3] NYU, Sch Med, Interdisciplinary Melanoma Cooperat Grp, New York, NY USA

[4] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA

[6] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal

[7] Programme Adv Med Educ, Lisbon, Portugal

来源：

CANCER IMMUNOLOGY RESEARCH | 2014年 / 2卷 / 05期

关键词：

NATURAL-KILLER-CELLS; CD8(+) T-CELLS; UP-REGULATION; TUMOR-CELLS; PD-1; EXPRESSION; RESPONSES; ANTIBODY; RECEPTOR; DEFINES;

D O I：

10.1158/2326-6066.CIR-13-0171

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The immunoregulatory protein T-cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell exhaustion and contributes to the suppression of immune responses in both viral infections and tumors. Tim-3 blockade reverses the exhausted phenotype of CD4(+) and CD8(+) T cells in several chronic diseases, including melanoma. Interestingly, natural killer (NK) cells constitutively express Tim-3; however, the role of Tim-3 in modulating the function of these innate effector cells remains unclear, particularly in human diseases. In this study, we compared the function of Tim-3 in NK cells from healthy donors and patients with metastatic melanoma. NK cells from the latter were functionally impaired/exhausted, and Tim-3 blockade reversed this exhausted phenotype. Moreover, Tim-3 expression levels were correlated with the stage of the disease and poor prognostic factors. These data indicate that Tim-3 can function as an NK-cell exhaustion marker in advanced melanoma and support the development of Tim-3-targeted therapies to restore antitumor immunity. (C) 2014 AACR.

引用

页码：410 / 422

页数：13

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