Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot, Nicolas; Enot, David P.; Flament, Caroline; Vimond, Nadège; Blattner, Carolin; Pitt, Jonathan M.; Yamazaki, Takahiro; 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; Dalle, Stéphane; Cavalcanti, Andréa; Kroemer, Guido; Di Giacomo, Anna Maria; Maio, Michele; Wong, Phillip; Yuan, Jianda; Wolchok, Jedd; Umansky, Viktor; Eggermont, Alexander; Zitvogel, Laurence

doi:10.1172/JCI80071

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Journal article

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot, Nicolas INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - University Paris-Saclay, Kremlin Bicêtre, France - Gustave Roussy Cancer Campus, Villejuif, France
Enot, David P. Gustave Roussy Cancer Campus, Villejuif, France - Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
Flament, Caroline INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France - CIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, France
Vimond, Nadège Gustave Roussy Cancer Campus, Villejuif, France - CIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, France - Laboratory of Immunomonitoring in Oncology (LIO), UMS 3655 CNRS, US 23 INSERM, Gustave Roussy Cancer Campus, Villejuif, France
Blattner, Carolin Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany - Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
Pitt, Jonathan M. INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France
Yamazaki, Takahiro INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France
Roberti, María Paula INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France
Daillère, Romain INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - University Paris-Saclay, Kremlin Bicêtre, France - Gustave Roussy Cancer Campus, Villejuif, France
Vétizou, Marie INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France
Poirier-Colame, Vichnou INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France
Semeraro, Michaëla INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Center of Clinical Investigation, Hôpital Necker Enfants Malades, Paris, France
Caignard, Anne INSERM U1016, CNRS UMR8104, Cochin Institute, Paris, France
Slingluff Jr., Craig L. Division of Surgical Oncology, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Rusakiewicz, Sylvie INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France - CIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, France
Weide, Benjamin Eberhard Karls Universität Tübingen, Department of Immunology, Tübingen, Germany - University Medical Center Tübingen, Department of Dermatology, Tübingen, Germany
Marabelle, Aurélien INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - Gustave Roussy Cancer Campus, Villejuif, France - CIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, France
Kohrt, Holbrook Division of Oncology, Department of Medicine, Stanford University, Stanford, California, USA
Dalle, Stéphane Centre Hospitalier Lyon-Sud, Cancer Research Center of Lyon and University Claude Bernard Lyon 1, Lyon, France
Cavalcanti, Andréa Gustave Roussy Cancer Campus, Villejuif, France
Kroemer, Guido Gustave Roussy Cancer Campus, Villejuif, France - Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France - Equipe 11 Labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France - INSERM, U1138, Paris, France - Université Paris Descartes, Sorbonne Paris Cité, Paris, France - Université Pierre et Marie Curie, Paris, France - Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
Di Giacomo, Anna Maria Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, Siena, Italy
Maio, Michele Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy
Wong, Phillip Ludwig Center for Cancer Immunotherapy, Department of Immunology and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Yuan, Jianda Ludwig Center for Cancer Immunotherapy, Department of Immunology and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Wolchok, Jedd Ludwig Center for Cancer Immunotherapy, Department of Immunology and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Umansky, Viktor Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany - Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
Eggermont, Alexander Gustave Roussy Cancer Campus, Villejuif, France
Zitvogel, Laurence INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France - University Paris-Saclay, Kremlin Bicêtre, France - Gustave Roussy Cancer Campus, Villejuif, France - CIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, France

08.02.2016

Published in:

The journal of clinical investigation. - 2016, vol. 126, no. 3, p. 921-937

English 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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