期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 126, 期 3, 页码 921-937出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI80071
关键词
-
资金
- Helmut Horten Foundation
- Institut National du Cancer
- Agence Nationale pour la Recherche
- Ligue contre le Cancer (equipe labellisee de L. Zitvogel)
- European Union (Inflammation and Cancer Research in Europe [INFLACARE])
- Site de Recherche Integree sur le Cancer (SOCRATES)
- LABEX OncoImmunology
- Direction Generale de l'Offre de Soins (Universite Paris-Sud)
- Paris Alliance for Cancer Research Institutes
- Association pour la Recherche sur le Cancer (ARC)
- Canceropole Ile-de-France
Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4(+) and CD8(+) T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8(+)CCR9(+) naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8(+) T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据