title: Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma.
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.
authors: Nicolas
authors: N
authors: Jacquelot
authors: David P
authors: DP
authors: Enot
authors: Caroline
authors: C
authors: Flament
authors: Nadège
authors: N
authors: Vimond
authors: Carolin
authors: C
authors: Blattner
authors: Jonathan M
authors: JM
authors: Pitt
authors: Takahiro
authors: T
authors: Yamazaki
authors: María Paula
authors: MP
authors: Roberti
authors: Romain
authors: R
authors: Daillère
authors: Marie
authors: M
authors: Vétizou
authors: Vichnou
authors: V
authors: Poirier-Colame
authors: Michaëla
authors: M
authors: Semeraro
authors: Anne
authors: A
authors: Caignard
authors: Craig L
authors: CL
authors: Slingluff
authors: Federica
authors: F
authors: Sallusto
authors: Sylvie
authors: S
authors: Rusakiewicz
authors: Benjamin
authors: B
authors: Weide
authors: Aurélien
authors: A
authors: Marabelle
authors: Holbrook
authors: H
authors: Kohrt
authors: Stéphane
authors: S
authors: Dalle
authors: Andréa
authors: A
authors: Cavalcanti
authors: Guido
authors: G
authors: Kroemer
authors: Anna Maria
authors: AM
authors: Di Giacomo
authors: Michele
authors: M
authors: Maio
authors: Phillip
authors: P
authors: Wong
authors: Jianda
authors: J
authors: Yuan
authors: Jedd
authors: J
authors: Wolchok
authors: Viktor
authors: V
authors: Umansky
authors: Alexander
authors: A
authors: Eggermont
authors: Laurence
authors: L
authors: Zitvogel
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009368:Neoplasm Transplantation; D016016:Proportional Hazards Models; D012372:ROC Curve; D019707:Receptors, Chemokine / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D019707:Receptors, Chemokine