1. Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma.
- Author
-
Jacquelot, Nicolas, Enot, David P., Flament, Caroline, Vimond, Nadège, Blattner, Carolin, Pitt, Jonathan M., Takahiro Yamazaki, Roberti, María Paula, Daillère, Romain, Vétizou, Marie, Poirier-Colame, Vichnou, Semeraro, Michaëla, Caignard, Anne, Slingluff Jr., Craig L., Sallusto, Federica, Rusakiewicz, Sylvie, Weide, Benjamin, Marabelle, Aurélien, Kohrt, Holbrook, and Dalle, Stéphane
- Subjects
- *
MELANOMA prognosis , *CHEMOKINE receptors , *T cells , *LYMPH node cancer , *PROTEIN expression , *PHYSIOLOGY , *ANIMAL experimentation , *ANIMALS , *ANTINEOPLASTIC agents , *CELL lines , *CELL receptors , *LUNG tumors , *MELANOMA , *METASTASIS , *MICE , *MONOCLONAL antibodies , *RESEARCH funding , *SKIN tumors , *PROPORTIONAL hazards models , *CASE-control method , *RECEIVER operating characteristic curves , *KAPLAN-Meier estimator , *PHARMACODYNAMICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF