Post date: Nov 18, 2016 2:12:12 PM
Jaime A. Espinoza, Shakila Jabeen, Richa Batra, Elena Papaleo, Vilde Haakensen, Vera Timmermans Wielenga, Maj-Lis Møller Talman, Nils Brunner, Anne-Lise Børresen-Dale, Pavel Gromov, Åslaug Helland, Vessela N. Kristensen,*, Irina Gromova*
Cytokine profiling of tumour interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics
The tumour 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 uncharacterised. Moreover, the data obtained regarding the origin of cytokine secretions, the levels of secretion associated with tumour development, and the possible clinical relevance of cytokines remain controversial. Therefore, we profiled 27 cytokines in 78 breast tumour 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--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 tumour infiltrating lymphocytes (TILs), while 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 was associated with a worse prognosis. These findings have important implications for BC immunotherapy research.
in press on OncoImmunology