Circulating levels of TNF- receptor II are prognostic for patients with peripheral T-cell Non-Hodgkin lymphoma
Menée à partir d'échantillons sanguins prélevés sur 117 patients atteints d'un lymphome T périphérique, cette étude montre que les niveaux sériques du récepteur II du TNF sont associés à la survie globale des patients
Background: Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHL with a poor outcome. Cytokines or their receptors might be associated with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNFRI (sTNFRI), sTNFRII, IL10 or sIL-4R are predictive for treatment response in T-NHL. Patients and methods: Peripheral blood DNA from 117 T-NHL patients treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained and circulating levels of sTNFRI, sTNFRII, IL-10 and sIL-4R, were determined with a specific capture enzyme-linked immunoassay. Results: Patients characterized by TNFRI-609GG (rs4149570) showed a trend towards better EFS (univariate p=0.041; multivariate HR: 1.76; CI: 0.99-3.14 with p=0.056).) A protective role of IL-10 -1087A, -824T, -597A, reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII ≥2,16ng/ml had a 2.07 fold increased relative risk for shorter overall survival (OS) (univariate p=0.0034; multivariate HR: 2.07; CI: 0.92-4.70 with p=0.081) and a 2.49 fold higher risk for shorter event free survival (EFS) (univariate p=0.00068; multivariate HR: 2.49; CI: 1.22-5.08 with p=0.012). Elevations of circulating levels of sTNFRI, IL-10 and sIL-4R are frequent, but the clinical response in these patients is not significantly different. Conclusions: Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHL.
Clinical Cancer Research , résumé, 2012