Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease

Frisan, Teresa; Sjøberg, Jan; Dolcetti, Riccardo; Boiocchi, Mauro; Re, Vallì De; Carbone, Antonino; Brautbar, Chaim; Battat, S.; Biberfeld, Peter; Eckman, M. K.

doi:10.1182/blood.v86.4.1493.bloodjournal8641493

Cited by 153 publications

(39 citation statements)

References 31 publications

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“…If HD patients are too immunocompromised to react against LMP-1, why do they not develop EBV-positive immunoblastomas, as seen in transplant recipients (Klein, 1992)? A possible explanation could be that EBV-specific cytotoxicity is suppressed locally in tumor tissue in EBV-positive patients, as reported by Frisan et al (1995). The mechanism behind this phenomenon, however, is unknown.…”

Section: Discussionmentioning

confidence: 86%

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

et al. 1997

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Section: Discussionmentioning

confidence: 86%

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

et al. 1997

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“…Elderly individuals are recognized to have lower immunocompetence than younger people. Elderly individuals may therefore have more difficulty in controlling the growth of an EBV-associated tumour than younger patients (Frisan et al, 1995;Armstrong et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Hodgkin's disease in the elderly: a population‐based study

Stark

Wood

Jack³

et al. 2002

Br J Haematol

137

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Summary. This study evaluated the incidence and outcome of Hodgkin's disease (HD) in older patients using a population-based approach. In total, 102 patients (52 men, 50 women) aged ‡ 60 years presented in the Northern Health Region of England (population of 3AE09 million) between 1 January 1991 and 31 December 1998 and were studied prospectively. The age-specific incidence was 1AE97/ 100 000 for those aged 60-69 years, and 2AE18/100 000 for those aged 70 years or over. The median age of the cohort was 70 years (range 60-91) and the median follow up was 63 months (range 20-113). Out of 95 treated patients, 70 (74%) obtained complete or good partial (> 90% response) remissions. In the 60 to 69-year-old group, the disease-specific survival at 5 years was 100% for those presenting with early stage disease and 52% for those with advanced stage disease. In patients aged >70 years the 5 year disease-specific survival was 36% in patients with early stage and 14% for patients with advanced stage disease. The survival of patients with Epstein-Barr virus (EBV)-positive tumours was significantly poorer than that of patients with EBV-negative tumours (P ¼ 0AE007); median survival in the former group was 20 months versus undefined in the latter group. In total, 43 deaths were due to progressive HD and five were treatment-related. This study defined the incidence of HD in our population and demonstrated that the prognosis of elderly patients, particularly those with advanced stage disease, has not improved concurrently with that of patients aged < 60 years old. Novel approaches to assessment and treatment are necessary.

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“…This substantial immunomodulating activity might be of relevance at least in the neighbourhood of reactivating cells. For EBV-pos cases of Hodgkin's disease, for example, it has been shown that the tumour cells secrete high levels of IL-10 leading to suppression of local immunity [24].…”

mentioning

confidence: 99%

The Primary and Memory Immune Response to Epstein–Barr Virus Infection In Vitro is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

et al. 2000

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Jabs WJ, Wagner HJ, Schlenke P, Kirchner H. The Primary and Memory Immune Response to EPSTEIN± BARR Virus Infection In Vitro is Characterized by a Divergent Production of IL-1b/IL-6 and IL-10. Scand J Immunol 2000;52:304±308 Reactivation of latent Epstein±Barr virus (EBV) infection is considered to exert substantial immunomodulating activities. Little is known about EBV's modulating activities on cytokine production upon primary, in contrast to reactivated, infection. Therefore, we investigated the cytokine production of latently infected EBV-positive (EBV-pos) adults upon in vitro EBV stimulation compared to nonimmune age-matched EBVnegative (EBV-neg) donors. Production of interleukin (IL)-1b and IL-6 was strongly decreased in peripheral blood mononuclear cell (PBMC) cultures of EBV-pos adults; in contrast, IL-10 and IL-1 receptor antagonist exhibited signi®cantly higher levels. As expected, interferon (IFN)-g production was almost exclusively observed in EBV-pos donors; it was accompanied by a signi®cantly higher IL-12 synthesis. Experiments employing T cell-depleted PBMC showed similar cytokine levels between EBV-pos and EBV-neg individuals suggesting that reactivation of EBV-speci®c memory T cells was responsible for the divergent cytokine pro®les. Production of viral IL-10 was excluded as a reason for higher IL-10 levels in EBV-pos individuals. In conclusion, our results do not appear to relate to any primary immunological differences between EBV-neg and EBV-pos adults, but show that the EBV-speci®c memory response to latent EBV infection is characterized by some anti-in¯ammatory effects. This might be of relevance upon reactivation of latent EBV infection in vivo and provides further evidence that EBV infection acts in an immunomodulating fashion.

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Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease

Cited by 153 publications

References 31 publications

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

Hodgkin's disease in the elderly: a population‐based study

The Primary and Memory Immune Response to Epstein–Barr Virus Infection In Vitro is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

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