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Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics.

ABSTRACT: Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines - the molecules coordinating and fine-tuning immune response - are still poorly characterized. Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the levels of 27 cytokines in the serum of breast cancer patients prior to treatment. We investigated the cytokine levels in relation to clinicopathological characteristics and in perspective of the tumor infiltrating immune cells predicted from the bulk mRNA expression data. Unsupervised clustering analysis of the serum cytokine levels in the MicMa cohort identified a cluster of pro-inflammatory, pro-angiogenic, and Th2-related cytokines which was associated with poor prognosis. Notably high levels of platelet derived growth factor BB (PDGF) reflected a more aggressive tumor phenotype and larger tumor size. A significant positive correlation between serum levels of interferon gamma-induced protein 10 (IP10) and its mRNA expression at the tumor site suggested that tumor-IP10-production may outflow to the bloodstream. High IP10 serum levels were associated with a worse prognosis. Finally, we found serum levels of both PDGF and IP10 associated with enrichment scores of specific tumor infiltrating immune cells. Our study suggests that monitoring cytokine circulating levels in breast cancer could be used to characterize breast cancers and the immune composition of their microenvironment through readily available biological material.

SUBMITTER: Jabeen S

PROVIDER: S-EPMC6343793 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics.

Jabeen Shakila S Espinoza Jaime A JA Torland Lilly Anne LA Zucknick Manuela M Kumar Surendra S Haakensen Vilde D VD Lüders Torben T Engebraaten Olav O Børresen-Dale Anne-Lise AL Kyte Jon Amund JA Gromov Pavel P Naume Bjørn B Kristensen Vessela V Gromova Irina I Tekpli Xavier X

Oncoimmunology 20181105 2

Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines - the molecules coordinating and fine-tuning immune response - are still poorly characterized. Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the leve ...[more]

PMID: 30713794

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Project description:BACKGROUND: The percentage of tumour stroma (TSP) has recently been reported to be a novel independent predictor of outcome in patients with a variety of common solid organ tumours. The aim of this study was to examine the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease. METHODS: A total of 361 patients with primary operable invasive ductal breast cancer were included in this study. The TSP was assessed visually on the haematoxylin and eosin-stained tissue sections. With a cutoff value of 50% TSP, patients with ≤ 50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group. RESULTS: A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had more Her-2-positive tumours (P=0.029), low-grade tumour inflammatory infiltrate (P=0.034), low CD68+macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter cancer-specific survival (P<0.001). In node-negative patients (n=207), high TSP was associated with low CD68+macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter cancer-specific survival (P=0.005). In triple negative patients (n=151), high TSP was associated with high tumour grade (P=<0.001), lymph node positivity (P=0.027), low CD68+macrophage infiltrate (P=0.011) and shorter cancer-specific survival (P=0.035). The 15-year cancer-specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. In multivariate survival analysis, a high TSP was associated with reduced cancer-specific survival in the whole cohort (P=0.001), node-negative patients (P=0.007) and those who received systemic adjuvant therapy (P=0.021), independent of other pathological characteristics including host inflammatory response. However, TSP was not an independent prognostic factor for triple negative patients (P=0.151). CONCLUSIONS: A high TSP in primary operable invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with primary operable ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with invasive ductal breast cancer.

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Dataset Information

Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics.

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Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics.

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