TY - JOUR
T1 - Chemokine receptor patterns in lymphocytes mirror metastatic spreaDing in melanoma
AU - Jacquelot, Nicolas
AU - Enot, David P.
AU - Flament, Caroline
AU - Vimond, Nadège
AU - Blattner, Carolin
AU - Pitt, Jonathan M.
AU - Yamazaki, Takahiro
AU - Roberti, María Paula
AU - Daillère, Romain
AU - Vétizou, Marie
AU - Poirier-Colame, Vichnou
AU - Semeraro, Michaëla
AU - Caignard, Anne
AU - Slingluff, Craig L.
AU - Sallusto, Federica
AU - Rusakiewicz, Sylvie
AU - Weide, Benjamin
AU - Marabelle, Aurélien
AU - Kohrt, Holbrook
AU - Dalle, Stéphane
AU - Cavalcanti, Andréa
AU - Kroemer, Guido
AU - DI Giacomo, Anna Maria
AU - Maio, Michele
AU - Wong, Phillip
AU - Yuan, Jianda
AU - Wolchok, Jedd
AU - Umansky, Viktor
AU - Eggermont, Alexander
AU - Zitvogel, Laurence
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84959879714
U2 - 10.1172/JCI80071
DO - 10.1172/JCI80071
M3 - Article
C2 - 26854930
AN - SCOPUS:84959879714
SN - 0021-9738
VL - 126
SP - 921
EP - 937
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -