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.
MeSH Terms
Antigens, CD20/metabolism
B-Lymphocytes/immunology,metabolism
B7-2 Antigen/metabolism
CD3 Complex/metabolism
CD4-Positive T-Lymphocytes/immunology,metabolism
CD8-Positive T-Lymphocytes/immunology,metabolism
Chemokines/genetics,metabolism
Gene Expression Profiling
Humans
Immunotherapy
Lymph Nodes/metabolism,pathology
Melanoma/mortality,pathology,therapy
Survival Analysis
Chemicals
Antigens, CD20
B7-2 Antigen
CD3 Complex
Chemokines
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Messina Jane L
Cutaneous Oncology, Moffitt Cancer Center , Tampa, FL, USA ; the Departments of Pathology and Cell Biology, University of South Florida , Tampa, FL, USA.
Fenstermacher David A
Eschrich Steven
Qu Xiaotao
Berglund Anders E
Lloyd Mark C
Schell Michael J
Sondak Vernon K
Weber Jeffrey S
Mulé James J
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