Lymphocyte function in untreated Hodgkin's disease: An important predictor of prognosis

Wedelin, Christina; Björkholm, Magnus; Holm, G.; Ogenstad, Stephan; Johansson, B.; Mellstedt, Håkan

doi:10.1038/bjc.1982.9

Cited by 35 publications

(12 citation statements)

References 30 publications

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“…In addition, cause-specific and overall survival was the same in these two patient groups respectively. As previously shown, increased spontaneous and decreased Con A induced blood lymphocyte DNA synthesis both predict a poor prognosis in HD (Björkholm et al, 1978;Wedelin et al, 1982;Tullgren et al, 1991). In addition, increased levels of sCD8 was associated with lymphocyte abnormalities and a dismal prognosis (Grimfors et al, 1992).…”

Section: Discussionmentioning

confidence: 66%

Epstein–Barr virus expression in Hodgkin’s disease in relation to patient characteristics, serum factors and blood lymphocyte function

et al. 1999

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Summary Epstein-Barr virus (EBV) expression was investigated by immunohistochemistry (latent membrane protein 1 ) and in situ hybridization (EBV encoded RNA [EBER]) in biopsies from 95 patients with untreated Hodgkin's disease (HD). Tumour EBV status was related to EBV antibody titres, spontaneous and concanavallin A induced blood lymphocyte DNA synthesis, serum levels of soluble (s) CD4, sCD8, sCD25, sCD30, sCD54, β2-microglobulin, thymidine-kinase, routine chemistry, patient characteristics, complete remission and survival. The median follow-up time was 145 months (range 60-257). Tumour EBV-positive (n = 30; 33%) and negative (n = 62; 67%) patients did not differ with regard to sex, age, stage, presence of bulky disease or B-symptoms, remission rate or survival. The proportion of EBV+ cases was significantly higher among patients with mixed cellularity histopathology (58%) as compared to the nodular sclerosis subtype (18%; P < 0.001). The total white blood cell (WBC) counts were significantly lower in EBV+ patients (P < 0.01), who also had significantly higher levels of sCD54 (P < 0.02) and a tendency towards lower levels of sCD30 (P = 0.056). Patients in the tumour EBV+ group had significantly higher IgG antibody titres to restricted early antigen (EA-R) (P < 0.02). Hence, clinical features and outcome were not related to tumour EBV status. However, HD patients with EBV+ tumours had elevated sCD54 levels, higher antibody titres to EA-R and decreased total WBC counts. A potential causal relationship between EBV tumour status and these findings needs to be further explored.

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Section: Discussionmentioning

confidence: 66%

Epstein–Barr virus expression in Hodgkin’s disease in relation to patient characteristics, serum factors and blood lymphocyte function

et al. 1999

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“…It is known that Hodgkin's lymphoma is associated with decreased cellular immunity (50,51) and that lymphocyte function influences the prognosis (52). Furthermore, it is known that monocytes produce increased amounts of PGE 2 in these patients (53,54).…”

Section: Pge 2 Leads To Inhibition Of Cd4mentioning

confidence: 99%

Prostaglandin E2 Impairs CD4+ T Cell Activation by Inhibition of lck: Implications in Hodgkin's Lymphoma

et al. 2006

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Many tumors, including Hodgkin's lymphoma, are associated with decreased cellular immunity and elevated levels of prostaglandin E 2 (PGE 2 ), a known inhibitor of CD4 + T cell activation, suggested to be involved in immune deviation in cancer. To address the molecular mechanisms tumor-derived PGE 2 might have on primary human CD4 + T cells, we used a whole genome-based transcriptional approach and show that PGE 2 severely limited changes of gene expression induced by signaling through the T cell receptor and CD28. This data suggests an interference of PGE 2 at an early step of T cell receptor signaling: indeed, PGE 2 stimulation of T cells leads to inactivation of lck and reduced phosphorylation of ZAP70. Antiapoptotic genes escaped PGE 2 -induced inhibition resulting in partial protection from apoptosis in response to irradiation or Fas-mediated signaling. As a functional consequence, PGE 2 -treated CD4 + T cells are arrested in the cell cycle associated with up-regulation of the cyclin/cyclin-dependent kinase inhibitor p27 kip1 . Most importantly, CD4 + T cells in Hodgkin's lymphoma show similar regulation of genes that were altered in vitro by PGE 2 in T cells from healthy individuals. These data strongly suggest that PGE 2 is an important factor leading to CD4 + T cell impairment observed in Hodgkin's lymphoma. (Cancer Res 2006; 66(2): 1114-22)

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“…Neverthekss, owing to the relatively small number of patients and short follow-up times, the ultimate prognostic value of this phenomenon has to be proven in a largr study, which is ongoing in our institute. Although previous studie on a similar question have failed to find such a prognostic value for PHA stimulation (Stein et al, 1976;Nordman et al, 1985) in solid tumours, it is an accepted predictive parameter in Hodgkin's disease (Bj6rkholm et al, 1982;Wedelin et al, 1982). However, the lack of such a finding in patients with solid tumours may be due to the heterogeneity of studied patients so far.…”

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confidence: 95%

Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study

Wiltschke

Krainer²,

Budinsky³

et al. 1995

Br J Cancer

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Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.

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Lymphocyte function in untreated Hodgkin's disease: An important predictor of prognosis

Cited by 35 publications

References 30 publications

Epstein–Barr virus expression in Hodgkin’s disease in relation to patient characteristics, serum factors and blood lymphocyte function

Epstein–Barr virus expression in Hodgkin’s disease in relation to patient characteristics, serum factors and blood lymphocyte function

Prostaglandin E2 Impairs CD4+ T Cell Activation by Inhibition of lck: Implications in Hodgkin's Lymphoma

Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study

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