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Espinoza, J.A.* ; Jabeen, S.* ; Batra, R. ; Papaleo, E.* ; Haakensen, V.* ; Timmermans Wielenga, V.* ; Talman, M.L.M.* ; Brunner, N.* ; Børresen-Dale, A.L.* ; Gromov, P.* ; Helland, Å.* ; Kristensen, V.N.* ; Gromova, I.*

Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics.

OncoImmunology 5:e1248015 (2016)

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	Open Access Green

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The tumor microenvironment is composed of many immune cell subpopulations and is an important factor in the malignant progression of neoplasms, particularly breast cancer (BC). However, the cytokine networks that coordinate various regulatory events within the BC interstitium remain largely uncharacterized. Moreover, the data obtained regarding the origin of cytokine secretions, the levels of secretion associated with tumor development, and the possible clinical relevance of cytokines remain controversial. Therefore, we profiled 27 cytokines in 78 breast tumor interstitial fluid (TIF) samples, 43 normal interstitial fluid (NIF) samples, and 25 matched serum samples obtained from BC patients with Luminex xMAP multiplex technology. Eleven cytokines exhibited significantly higher levels in the TIF samples compared with the NIF samples: interleukin (IL)-7, IL-10, fibroblast growth factor-2, IL-13, interferon (IFN)γ-inducible protein (IP-10), IL-1 receptor antagonist (IL-1RA), platelet-derived growth factor (PDGF)-β, IL-1β, chemokine ligand 5 (RANTES), vascular endothelial growth factor, and IL-12. An immunohistochemical analysis further demonstrated that IL-1RA, IP-10, IL-10, PDGF-β, RANTES, and VEGF are widely expressed by both cancer cells and tumor-infiltrating lymphocytes (TILs), whereas IP-10 and RANTES were preferentially abundant in triple-negative breast cancers (TNBCs) compared to Luminal A subtype cancers. The latter observation corresponds with the high level of TILs in the TNBC samples. IL-1β, IL-7, IL-10, and PDGFβ also exhibited a correlation between the TIF samples and matched sera. In a survival analysis, high levels of IL-5, a hallmark TH2 cytokine, in the TIF samples were associated with a worse prognosis. These findings have important implications for BC immunotherapy research.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Array ; Breast Cancer ; Cytokine ; Growth Factor ; Interleukin ; Interstitial Fluid ; T 2 H ; Tumor-infiltrating Lymphocyte; Regulatory T-cells; Colorectal-cancer; Preferential Expansion; Interleukin-7 Il-7; Chemokine Cxcl10; Expression; Microenvironment; Metastasis; Progression; Carcinoma

ISSN (print) / ISBN 2162-4011

e-ISSN 2162-402X

Journal OncoImmunology

Quellenangaben Volume: 5, Issue: 12, Article Number: e1248015

Publisher Taylor & Francis

Publishing Place Philadelphia

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)