Hodgkin's disease: a tumor with disturbed immunological pathways

Gruss, Hans Jürgen; Pinto, Antonio; Duyster, Justus; Poppema, Sibrand; Herrmann, F

doi:10.1016/s0167-5699(97)84661-0

Cited by 127 publications

(129 citation statements)

References 54 publications

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“…The conclusion of this study is that constitutive activation of NF-kB observed in Hodgkin cell lines (Bargou et al, 1996;Gruss et al, 1997; this study) is a consequence of defective IkBa. In KM-H2 cells IkBa cannot be detected under normal circumstances, but an 18 kD fragment of IkBa is detected after treatment of the cells with an inhibitor of proteasomal degradation ( Figure 5).…”

Section: Discussionmentioning

confidence: 70%

“…They produce a large number of cytokines including interleukin-1a (IL-1), tumour necrosis factor (TNFa) and lymphotoxin-a (LTa) which are associated with the constitutional or B' symptoms of Hodgkin's disease ± fever, night sweats, itching and weight loss (Gorschluter et al, 1995;Gruss et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…A common feature of Reed-Sternberg and Hodgkin cells is that they have high levels of constitutively active NF-kB (Bargou et al, 1996;Gruss et al, 1997). The NF-kB family of transcription factors plays a crucial role in the activation of many genes, the products of which have important roles in cell proliferation, the immune response and in¯ammation.…”

Section: Introductionmentioning

confidence: 99%

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Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

1998

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

1998

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“…Furthermore, in a significant portion of cases, HRS cells infected by EBV also commonly express LMP1 proteins (32,33). Interestingly, HRS cells not only express TNFR proteins but also produce several ligands for these receptors as well, including TNF-␣, TNF-␤, LT-␣, and CD30L (26,28,29,37,39,40). Thus, HRS cells may be capable of autoamplifying TNFR stimulatory signaling via autocrine and paracrine receptorligand interaction.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

et al. 2000

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“…Active accumulation of these reactive cells, which include lymphocytes, eosinophils, monocytes, neutrophils and fibroblasts, is dependent upon antigen presentation and activation of HRS cells and bystander reactive cells (Gruss et al, 1997). In the majority of cases HRS cells are believed to derive from germinal centre or post-germinal centre B cells that carry non-functional V H gene rearrangements, suggesting that HRS cells can bypass the apoptosis that would otherwise eliminate B cells with defectively rearranged Ig genes (Hummel et al, 1995;Kanzler et al, 1996).…”

mentioning

confidence: 99%

Assessment of the prognostic impact of the Epstein–Barr virus-encoded latent membrane protein-1 expression in Hodgkin’s disease

et al. 2001

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SummaryWe have examined expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) and its impact on response to treatment and on survival. Paraffin tissue from 100 adult immunocompetent patients with HD were analysed using immunohistochemistry to identify LMP1 expression. According to the Rye classification, 8% of patients had lymphocyte predominance (LP) subtype, 48% had nodular sclerosis (NS) disease, 37% were of the mixed cellularity (MC) subtype and 7% were of the lymphocyte depletion (LD) subtype. During the five year follow-up period 27 patients died and 74 patients achieved a complete remission. Patients with LD subtype were older (P = 0.03), less frequently achieved complete remission (P = 0.01), had shorter disease-free survival (P = 0.01) and overall survival (P = 0.002) compared with the other subtypes of HD. LMP1 expression was found in the tumour cells of 26% of cases of HD. LMP1 expression was less common in NS disease than in the other subtypes (P = 0.05), whereas an association between MC subtype and LMP1 expression was not found (P = 0.22). Using the log-rank test there were no differences in overall survival or disease-free survival based on EBV status either when all patients were analysed or when LD and LP subtypes were excluded. However, the presence of EBV was associated with significantly longer disease-free survival in the subgroup of patients ≤ 30 years old (P = 0.02) and in those patients ≤ 34 years old (P = 0.05). In contrast, there was a trend for shorter disease-free survival for EBV-positive patients in the subgroup > 35 years old, but this difference was not statistically significant (P = 0.11). A similar trend was observed in patients > 50 years old. Analysis of the impact of LMP1 expression in patients who had different stage and B symptoms status showed that expression of EBV was associated with longer disease-free survival (P = 0.019) in early stage (1 + 2) patients without B symptoms. Significant differences in the other subgroups based on EBV status was not found. Factors adversely affecting the likelihood to achieve a complete remission were: absence of LMP1 expression (OR 6.4, 95% Cl 1.07-38.5, P = 0.04), age (OR 1.68, 95%Cl 1.15-2.5, P = 0.007) and subtype of HD (OR 3.32, 95%Cl 1.11-9.94, P = 0.03). Age and subtype of HD had an independent impact on overall survival (P = 0.01). We conclude that expression of LMP1 in HRS cells has a favourable impact on prognosis for HD patients, but that this effect may be restricted to young adult patients and those with early stage disease.

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Hodgkin's disease: a tumor with disturbed immunological pathways

Cited by 127 publications

References 54 publications

Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Assessment of the prognostic impact of the Epstein–Barr virus-encoded latent membrane protein-1 expression in Hodgkin’s disease

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