Plasma Cytokine and Soluble Receptor Signature Predicts Outcome of Patients With Classical Hodgkin's Lymphoma: A Study From the Groupe d'Etude des Lymphomes de l'Adulte

Casasnovas, Olivier; Mounier, Nicolas; Brice, Pauline; Diviné, Marine; Morschhauser, Franck; Gabarre, Jean; Blay, Jean‐Yves; Voillat, Laurent; Léderlin, P.; Stamatoullas, Aspasia; Bienvenu, Jacques; Guiguet, Michel; Intrator, L; Grandjean, Monique; Brière, Josette; Fermé, Christophe; Salles, Gilles

doi:10.1200/jco.2006.08.1331

Cited by 105 publications

(75 citation statements)

References 32 publications

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“…Our findings are similar to cytokine signatures that are associated with poor survival after sepsis (14,15) and cancer (16). We also found that elevated TNFR-I on day 8 was strongly associated with mortality, and lower concentrations were associated with renal recovery.…”

Section: Discussionsupporting

confidence: 86%

Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes

Murugan

Wen

Keener

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Critically ill patients requiring RRT have higher circulating plasma concentrations of inflammatory and apoptosis markers that are associated with subsequent RRT dependence and death. Whether intensive dosing of RRT is associated with changes in specific mediators is unknown.Design, setting, participants, & measurements A multicenter, prospective, cohort study of 817 critically ill patients receiving RRT ancillary to the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study was conducted between November 2003 and July 2007. Plasma inflammatory (IL-6, IL-8, IL-10, IL-18, and macrophage migration inhibitory factor) and apoptosis (TNF receptor-I [TNFR-I], TNFR-II, and death receptor-5) biomarkers on days 1 and 8 were examined after initiation of intensive RRT. Whether intensive RRT, given day 1 biomarkers, is associated with RRT independence and lower mortality at day 60 was also examined.Results Overall, no differences were found in day 8 biomarker concentrations between intensive and lessintensive RRT groups. When adjusted for day 1 biomarkers and clinical variables, intensive RRT was not associated with renal recovery (adjusted odds ratio [OR], 0.80; 95% confidence interval, 0.56 to 1.14) or mortality (adjusted OR, 1.15; 95% confidence interval, 0.81 to 1.64). Use of intensive RRT, however, was associated with lower day 8 concentrations when day 1 plasma IL-6, macrophage migration inhibitory factor, and TNFR-I concentrations were high (interaction P value for all markers, ,0.01). In contrast, day 8 marker concentrations were higher when day 1 levels were low (P,0.01). Elevated biomarker concentrations on day 8 among 476 participants were associated with lower renal recovery (adjusted OR range, 0.19-0.87) and higher mortality (adjusted OR range, 1.26-3.18).Conclusions Among critically ill patients receiving RRT, intensive dosing of RRT has variable association with biomarker concentration and no association with renal recovery and mortality. However, elevated concentrations of inflammatory and apoptosis markers on day 8 of RRT were associated with RRT dependence and death.

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Section: Discussionsupporting

confidence: 86%

Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes

Murugan

Wen

Keener

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…These mediators can be used as potential prognostic factors during treatment [61][62][63]. Because the HL microenvironment consists of 20%-50% of reactive, polyclonal B cells, elevated serum-free light chain levels can be detected in approximately 30% of the patients and can be predictive of treatment outcome [64].…”

Section: Microenvironmentmentioning

confidence: 99%

Immunologic pathomechanism of Hodgkin's lymphoma

Jóna

Szodoray

Illés

2013

Experimental Hematology

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“…21 In a recent study, Casasnovas et al also demonstrated that the plasma cytokine signature could be used to predict diseaserelated outcome in cHL. 22 For the proteins identified in this study, additional large-scale studies on HL patient plasma or serum need to be performed to elucidate the possible relation of the 7 potential biomarkers to disease activity.The main goal of this study was to identify new players that might contribute to the pathogenesis of HL. For the chemokines TARC, RANTES, and IP-10, previous studies already demonstrated their putative role and confirmed expression in HRS cells of patient tissues.…”

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confidence: 99%

Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

Yue¹,

Visser²,

Roelofsen³

et al. 2008

Blood

117

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IntroductionHodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the Hodgkin and Reed-Sternberg cells (HRS cells), and an extensive inflammatory background. Many studies have documented that HL is associated with disturbed cytokine production. 1 Cytokine and chemokine production may not only promote growth of HRS cells and help to evade immune surveillance, but also cause the characteristic histology and the clinical symptoms of HL. 2 Cross-talk between HRS cells and surrounding lymphocytes has been studied for many years, and this interaction is regarded to be important for the pathogenesis of HL.The application of proteomics techniques has been proven to be a powerful tool for the identification of new biomarkers involved in pathogenesis of many diseases (reviewed by Hanash 3 ). Some studies on hematologic malignancies using proteomics approaches have been reported, 4,5 but application of proteomics technology to HL is still limited. Fujii et al compared HL cell line proteome to anaplastic large cell lymphoma (ALCL) and non-Hodgkin lymphoma (NHL) using a 2-dimensional difference gel electrophoresis approach of total cell lysates. 6,7 HL expressed higher levels of pyridoxine-5Ј-phosphate oxidase, vinculin, dihydropyrimidinase-related protein-2 and NADHubiquinone oxidoreductase compared with ALCL. In comparison to NHL cell lines, HL cell lines showed higher expression of pyridoxine-5Ј-phosphate oxidase, ␥-enolase, vinculin, vimentin, galectin-1, annexin A5, and protein kinase C substrate. 7 Carvalho et al identified changes in the spectrum using quadrupole-time-of-flight hybrid mass spectrometer in serum of HL patients compared with normal controls, but no further protein identification was performed. 8 Overall, only very limited proteomics data are available for HL.To gain more insight into the proteins secreted by HRS cells that might be involved in the cross-talk with infiltrating lymphocytes or might serve as tumor biomarkers, the secretome of HL cell lines was determined in cell culture supernatant. Protein identification was performed by nanoscale reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) after 1D-SDS-PAGE fractionation. Proteins related to immune response were validated in cell culture supernatant and patient plasma by enzyme-linked immunosorbent assay (ELISA) and in tumor tissues by immunohistochemistry. Methods Cell lines and cultureThe HL cell lines L1236 and KMH2 were established from HL patients with mixed cellularity subtype, L428 from nodular sclerosis subtype and DEV from nodular lymphocyte predominant HL (NLPHL) subtype. They were cultured in RPMI 1640 medium (Lonza Walkersville, Walkersville, MD) supplemented with fetal calf serum (Lonza Walkersville). For analysis of secreted proteins, to avoid the masking effects of high-abundance serum proteins in the culture medium, the cells were washed 3 times with RPMI 1640 medium to deplete all serum proteins, and cultured in RPMI 1640 medium without serum for 24 hours. Under these conditions, cell via...

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Plasma Cytokine and Soluble Receptor Signature Predicts Outcome of Patients With Classical Hodgkin's Lymphoma: A Study From the Groupe d'Etude des Lymphomes de l'Adulte

Cited by 105 publications

References 32 publications

Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes

Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes

Immunologic pathomechanism of Hodgkin's lymphoma

Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

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