Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma - Sorbonne Université Access content directly
Journal Articles Journal of Clinical Investigation Year : 2016

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Anne Caignard
  • Function : Author
Craig L. Slingluff Jr.
  • Function : Author
  • PersonId : 899131
Holbrook E Kohrt
  • Function : Author
  • PersonId : 958269
Michele Maio
  • Function : Author
  • PersonId : 899117
Phillip Wong
  • Function : Author
Jianda Yuan
  • Function : Author
Jedd Wolchok
  • Function : Author
  • PersonId : 924533
Alexander Eggermont
  • Function : Author
  • PersonId : 942521

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.
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hal-01295136 , version 1 (01-04-2016)

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Nicolas Jacquelot, David P. Enot, Caroline Flament, Nadège Vimond, Carolin Blattner, et al.. Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma. Journal of Clinical Investigation, 2016, 126 (3), pp.921-937. ⟨10.1172/JCI80071⟩. ⟨hal-01295136⟩
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