title: 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?
abstract: We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20⁺ B cell follicles with prominent areas of CD3⁺ T cells (both CD4⁺ and CD8⁺ subsets). CD86⁺, but not FoxP3⁺, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.
authors.affiliation: Cutaneous Oncology, Moffitt Cancer Center , Tampa, FL,  USA ; the Departments of Pathology and Cell Biology, University of South Florida , Tampa, FL,  USA.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Messina
authors.forename: David A
authors.initials: DA
authors.lastname: Fenstermacher
authors.forename: Steven
authors.initials: S
authors.lastname: Eschrich
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Qu
authors.forename: Anders E
authors.initials: AE
authors.lastname: Berglund
authors.forename: Mark C
authors.initials: MC
authors.lastname: Lloyd
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schell
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: James J
authors.initials: JJ
authors.lastname: Mulé
mesh_terms: D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007167:Immunotherapy; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D018951:Antigens, CD20; D051940:B7-2 Antigen; D017252:CD3 Complex; D018925:Chemokines