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PMID: 23097687 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Scientific reports ·Vol. 2 ·2012-00-00 ·Pages 765

Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, Schell MJ, Sondak VK, Weber JS, Mulé JJ

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
References (21)
21 references, click to expand
  1. Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.
    J Immunol. 2008 Sep 1;181(5):3524-34 PMID: 18714025
  2. Ectopic lymph nodes within human solid tumors.
    J Clin Oncol. 2008 Sep 20;26(27):4369-70 PMID: 18802146
  3. On the eve of personalized medicine in oncology.
    Cancer Res. 2008 Sep 15;68(18):7250-2 PMID: 18794109
  4. Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity.
    Exp Biol Med (Maywood). 2011 May 1;236(5):567-79 PMID: 21486861
  5. Immune infiltration in human cancer: prognostic significance and disease control.
    Curr Top Microbiol Immunol. 2011;344:1-24 PMID: 20512556
  6. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling.
    Am J Pathol. 2011 Jul;179(1):37-45 PMID: 21703392
  7. CCR6 regulates the migration of inflammatory and regulatory T cells.
    J Immunol. 2008 Dec 15;181(12):8391-401 PMID: 19050256
  8. Human T-lymphotropic virus type 1-induced CC chemokine ligand 22 maintains a high frequency of functional FoxP3+ regulatory T cells.
    J Immunol. 2010 Jul 1;185(1):183-9 PMID: 20525891
  9. The dynamics of the T-cell antitumor response: chemokine-secreting dendritic cells can prime tumor-reactive T cells extranodally.
    Cancer Res. 2001 Dec 15;61(24):8794-802 PMID: 11751401
  10. Analysis of T-cell clonality using laser capture microdissection and high-resolution microcapillary electrophoresis.
    J Mol Diagn. 2007 Sep;9(4):490-7 PMID: 17620388
  11. Recent advances using anti-CTLA-4 for the treatment of melanoma.
    Cancer J. 2009 May-Jun;15(3):169-73 PMID: 19556898
  12. Cancer and the chemokine network.
    Nat Rev Cancer. 2004 Jul;4(7):540-50 PMID: 15229479
  13. Chemokines: can effector cells be redirected to the site of the tumor?
    Cancer J. 2010 Jul-Aug;16(4):325-35 PMID: 20693843
  14. Two hundred years of cancer research.
    N Engl J Med. 2012 Jun 7;366(23):2207-14 PMID: 22646510
  15. Blockade of CCL1 inhibits T regulatory cell suppressive function enhancing tumor immunity without affecting T effector responses.
    J Immunol. 2010 Jun 15;184(12):6833-42 PMID: 20483762
  16. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.
    Clin Cancer Res. 2011 Jul 1;17(13):4550-7 PMID: 21498393
  17. Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade.
    Semin Oncol. 2010 Oct;37(5):430-9 PMID: 21074057
  18. The blockade of immune checkpoints in cancer immunotherapy.
    Nat Rev Cancer. 2012 Mar 22;12(4):252-64 PMID: 22437870
  19. The immune score as a new possible approach for the classification of cancer.
    J Transl Med. 2012 Jan 03;10:1 PMID: 22214470
  20. The many roles of chemokines and chemokine receptors in inflammation.
    N Engl J Med. 2006 Feb 9;354(6):610-21 PMID: 16467548
  21. Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal.
    Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5560-5 PMID: 21415369
Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
Published
2012-00-00
Epub
2012-00-24
Pages
765
Language
English
Region
England
NLM ID
101563288
PMCID
PMC3479449
Subset
IM
Grants
NCI NIH HHS · P30 CA076292 · United States
NCI NIH HHS · R01 CA148995 · United States
NCI NIH HHS · 1R01 CA148995-01 · United States
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