Chemokine receptor patterns in lymphocytes mirror metastatic spreaDing in melanoma

Nicolas Jacquelot, David P. Enot, Caroline Flament, Nadège Vimond, Carolin Blattner, Jonathan M. Pitt, Takahiro Yamazaki, María Paula Roberti, Romain Daillère, Marie Vétizou, Vichnou Poirier-Colame, Michaëla Semeraro, Anne Caignard, Craig L. Slingluff, Federica Sallusto, Sylvie Rusakiewicz, Benjamin Weide, Aurélien Marabelle, Holbrook Kohrt, Stéphane DalleAndréa Cavalcanti, Guido Kroemer, Anna Maria DI Giacomo, Michele Maio, Phillip Wong, Jianda Yuan, Jedd Wolchok, Viktor Umansky, Alexander Eggermont, Laurence Zitvogel

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    62 Citations (Scopus)

    Résumé

    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 CLAexpressing 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.

    langue originaleAnglais
    Pages (de - à)921-937
    Nombre de pages17
    journalJournal of Clinical Investigation
    Volume126
    Numéro de publication3
    Les DOIs
    étatPublié - 1 mars 2016

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