12-Chemokine Gene Signature Identifies Lymph Node-like Structures in Melanoma: Potential for Patient Selection for Immunotherapy?
Open accessAbstract
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.
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A 12-chemokine gene expression signature uncovers the presence of tumor-localized tertiary lymphoid structures, which positively correlate with overall survival in certain patients with metastatic melanoma.
“they are also included in a 12-chemokine gene expression signature that we have shown to uncover the presence of the tumor-localized, tertiary lymphoid structures, which are found to positively correlate with overall survival in certain patients with metastatic melanoma33.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [33]
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- Authors
- Messina, J. L., Fenstermacher, D. A., Eschrich, S., Qu, X., Berglund, A. E., Lloyd, M. C., Schell, M. J., Sondak, V. K., Weber, J. S., & Mulé, J. J.
- Affiliations
- University of South Florida (US)
- Moffitt Cancer Center (US)
- Corresponding author
- Mulé, James J.
- ORCID
- Venue
- Scientific Reports
- Published
- 2012-10-24
- Volume
- 2
- Issue
- 1
- Pages
- 765-765
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3479449
- OpenAlex
- W2020627452
- Cited by
- 426
- References
- 2
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 55 · 2023: 42 · 2022: 35 · 2021: 45 · 2020: 28 · 2019: 18 · 2018: 30 · 2017: 27 · 2016: 23 · 2015: 21 · 2014: 25 · 2013: 23
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- V Foundation for Cancer Research
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health
- National Cancer Institute (R01CA148995, P30CA076292)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- melanoma metastasis, CD3+ T cells, CD86, Foxp3, tumor-infiltrating lymphocytes, antitumor immunity, immunotherapy selection, overall survival, gene expression signatures
- MeSH terms
- B-Lymphocytes, Humans, Immunotherapy, Lymph Nodes, Melanoma, CD4-Positive T-Lymphocytes, Survival Analysis, CD3 Complex, CD8-Positive T-Lymphocytes, Chemokines, Antigens, CD20, Gene Expression Profiling, B7-2 Antigen
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