Circulating Levels of TNF Receptor II Are Prognostic for Patients with Peripheral T-cell Non–Hodgkin Lymphoma

Heemann, Christina; Kreuz, Markus; Stoller, Irene; Schoof, Nils; Bonin, Frederike von; Ziepert, Marita; Löffler, Markus; Jung, Wolfram; Pfreundschuh, Michael; Trümper, Lorenz; Kube, Dieter

doi:10.1158/1078-0432.ccr-11-3299

Cited by 33 publications

(29 citation statements)

References 54 publications

(73 reference statements)

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“…The levels of sTNF-R1 and sTNF-R2 in the vascular circulation are increased significantly with age and altered in obese individuals [2–4] and chronic inflammatory conditions and diseases [5–8] as well as several cancers [9–15]. Although correlations with the clinical stage, risk of progression, and the risk of developing certain cancers have been described [9–16] there is very little information on the levels of these soluble receptors in glioblastoma and their potential clinical relevance in GBM.…”

Section: Introductionmentioning

confidence: 99%

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma

et al. 2016

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The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p=0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients.

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Section: Introductionmentioning

confidence: 99%

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma

et al. 2016

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“…In previous years, it was reported that TNFR2 has important roles in the occurrence and progression of various types of tumor, including skin tumors, cholangiocarcinoma, myeloma, colorectal cancer and non-Hodgkin lymphoma (13)(14)(15)(16)(17). Jöhrer et al reported that high expression of TNFR2 promoted the metastasis of myeloma cells (15).…”

Section: Discussionmentioning

confidence: 99%

“…It was initially identified in hematopoietic cells and endothelial cells, and is involved in anti-inflammation, immune regulation, the repair of lung injury induced by lipopolysaccharide and the healing of bone fracture (10)(11)(12). The high expression of TNFR2 and its pro-progression roles have been previously reported in various types of tumor, including skin tumors, cholangiocarcinoma, myeloma, colorectal cancer and non-Hodgkin lymphoma (13)(14)(15)(16)(17). However, in BC, clinical studies about TNFR2 were mainly focused on sTNFR2 in the blood, and the clinical implication of TNFR2 in BC tissue remains limited (18,19).…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of tumor necrosis factor receptor 2 in breast cancer

Yang

Zhao

Zhao³

2017

Oncology Letters

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Abstract. Tumor necrosis factor receptor 2 (TNFR2) is a member of the tumor necrosis factor receptor family. Its high expression and oncogenic roles have been reported in several types of tumors in previous years. However, the clinical implication of TNFR2 in breast cancer (BC) tissue (i.e., not soluble TNFR2 in blood or genetic variation of TNFR2) has not been reported. In the present study, TNFR2 expression was detected in BC tissue using immunohistochemistry and, to the best of our knowledge, it was confirmed for the first time that TNFR2 was positively associated with increased tumor size, advanced clinical stage and higher pathological grade. Survival analysis revealed that TNFR2 was positively associated with shorter overall survival (OS) time and disease-free survival (DFS) time. In addition, univariate regression analysis demonstrated that TNFR2 expression (P=0.045), tumor size (P<0.0001), clinical stage (P<0.0001), pathological grade (P=0.002), estrogen and progesterone receptor and human epidermal growth factor receptor 2 (HER2) triple-status (P=0.001) all had a significant impact on the OS rate of patients with BC. TNFR2 expression (P=0.017), age (P=0.011), menopausal status (P<0.0001), tumor size (P=0.016), clinical stage (P=0.005), pathological grade (P=0.002) and estrogen/progesterone receptor and HER2 triple-status (P=0.008) were all shown to significantly impact the DFS rate of patients with BC. Multivariate regression analysis showed that only clinical stage (P=0.024), estrogen and progesterone receptor status and HER2 status (P=0.009) had a significant impact on the OS rate of patients with BC, while TNFR2 expression (P=0.043) and menopausal status (P=0.033) were shown to significantly impact the DFS rate of patients with BC. These data indicated that TNFR2 may perform important roles in the progression and prognosis of BC. This enriches previous understanding about TNFR2 in BC.

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“…For example, the T allele was significantly associated with systemic lupus erythematous [38], poor survival outcomes in non-small-cell lung cancers [39], and T cell non-Hodgkin's lymphoma [40]; however, this polymorphism was protective against oral carcinoma [41], which decreased the risk of colon cancer [42] and invasive pulmonary aspergillosis [43]. Kim et al [44] found out that the TNFRI −609G/T polymorphism was strongly associated with primary hepatocellular carcinoma and that the T allele repressed TNFRI expression.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Tumor Necrosis Factor Receptor Genes Affect the Expression Levels of Membrane-Bound Type I and Type II Receptors

Sennikov

Vasilev

Lopatnikova

et al. 2014

Mediators of Inflammation

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The level of TNF receptors on various cells of immune system and its association with the gene polymorphism were investigated. Determining the levels of membrane-bound TNFα receptors on peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry using BD QuantiBRITE calibration particles. Soluble TNFα receptor (sTNFRs) levels were determined by ELISA and genotyping was determined by PCR-RFLP. Homozygous TT individuals at SNP −609G/T TNFRI (rs4149570) showed lower levels of sTNFRI compared to GG genotype carriers. Homozygous carriers of CC genotype at SNP −1207G/C TNFRI (rs4149569) had lower expression densities of membrane-bound TNFRI on intact CD14+ monocytes compared to individuals with the GC genotype. The frequency differences in the CD3+ and CD19+ cells expressing TNFRII in relation to SNP −1709A/T TNFRII (rs652625) in healthy individuals were also determined. The genotype CC in SNP −3609C/T TNFRII (rs590368) was associated with a lower percentage of CD14+ cells expressing TNFRII compared to individuals with the CT genotype. Patients with rheumatoid arthritis had no significant changes in the frequencies of genotypes. Reduced frequency was identified for the combination TNFRI −609GT + TNFRII −3609CC only. The polymorphisms in genes represent one of cell type-specific mechanisms affecting the expression levels of membrane-bound TNFα receptors and TNFα-mediated signaling.

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Circulating Levels of TNF Receptor II Are Prognostic for Patients with Peripheral T-cell Non–Hodgkin Lymphoma

Cited by 33 publications

References 54 publications

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma

Clinical implications of tumor necrosis factor receptor 2 in breast cancer

Polymorphisms in the Tumor Necrosis Factor Receptor Genes Affect the Expression Levels of Membrane-Bound Type I and Type II Receptors

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