12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

Sci Rep. 2012;2:765. doi: 10.1038/srep00765. Epub 2012 Oct 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD20 / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B7-2 Antigen / metabolism
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemokines / genetics*
  • Chemokines / metabolism
  • Gene Expression Profiling
  • Humans
  • Immunotherapy
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Melanoma / mortality
  • Melanoma / pathology
  • Melanoma / therapy*
  • Survival Analysis

Substances

  • Antigens, CD20
  • B7-2 Antigen
  • CD3 Complex
  • Chemokines