Serum IL-6, IL-8, IL-10 and Beta<sub>2</sub>-Microglobulin in Association with International Prognostic Index in Diffuse Large B Cell Lymphoma

Duletić-Načinović, Antica; Štifter, Sanja; Marijić, Blažen; Lučin, Ksenija; Valković, Toni; Petranović, Duška; Jonjić, Nives

doi:10.1177/030089160809400412

Cited by 23 publications

(22 citation statements)

References 34 publications

(52 reference statements)

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“…[40][41][42][43] In addition, IL-6, IL-10, and VEGF can affect myeloid differentiation, activation, and trafficking. [44][45][46][47] IL-10 has also been shown to sequester HLA-DR in monocytes.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Lin

Gustafson

Bulur

et al. 2011

Blood

226

225

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Immunosuppression is a known risk factor for B-cell non-Hodgkin lymphoma (NHL), yet mechanisms of tumor-associated immunosuppression remain to be fully characterized. We examined the immunophenotype of 40 NHL patients and 27 age-matched healthy volunteers to better understand systemic immune suppression. NHL peripheral blood mononuclear cells had significantly decreased interferon-␥ production and proliferation. This suppression was not the result of regulatory T cells, interleukin-6 or interleukin-10, as these factors were not different between NHL and healthy volunteers (controls). We were able to restore T-cell proliferation by removing NHL monocytes, suggesting that these monocytes are suppressive. This suppression was mediated in part through arginine metabolism as exogenous arginine supplementation partially overcame monocytes' suppression of T-cell proliferation in vitro and NHL patients had elevated arginase I in their plasma. NHL monocytes had impaired STAT1 phosphorylation and interferon-␣ production to CpG stimulation and a dendritic cell differentia- IntroductionSystemic immune suppression is often seen in cancer patients and is thought to contribute to patient morbidity via tumor-mediated immune evasion. Indeed, patients with compromised immune systems, such as those with HIV infection, or on immunosuppressive medications are at increased risk of developing non-Hodgkin lymphoma (NHL). 1,2 Polymorphisms in host germline immune genes also have been associated with risk of developing NHL 3 as well as survival in NHL patients. 4 Conversely, a small percentage of patients with indolent NHL have spontaneous regression of their disease without any treatment, 5 possibly linked to a host antitumor immune response. The presence of host immune cells in the tumor microenvironment has also been correlated with treatment outcome and survival. [6][7][8][9] Of note, reduction in absolute count of circulating lymphocytes has been identified as a poor prognostic factor for overall survival in newly diagnosed NHL 10,11 as well as a predictor of poor treatment response. 9,12,13 Although evidence for the role of immune suppression in tumor establishment and pathogenesis is unquestionable, the mechanisms and the cellular phenotype of systemic immune suppression in NHL patients remain to be fully characterized.In this study, we investigated the qualitative and quantitative systemic immune suppression in B-cell NHL. We found circulating mononuclear cells had suppressed interferon-␥ (IFN-␥) recall response and proliferative capacity. These suppressed functions were mediated by circulating monocytes and partly mediated via arginine metabolism. These monocytes also had other impaired adaptive immune response including a decreased capacity to generate mature dendritic cells. In addition, the innate immune response of these monocytes to CpG stimulation was impaired as measured by intracellular STAT1 phosphorylation and interferonalpha (IFN-␣) production. These multifactorial suppressive functions of monocytes in NHL were corre...

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Lin

Gustafson

Bulur

et al. 2011

Blood

226

225

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“…A standardized laboratory method with good performance, i.e., the electrochemiluminescence immunoassay (ECLIA), was used to determine the cytokine levels. In addition, studies suggest that increased serum IL-8 and tumor necrosis factor α (TNF-α) levels are correlated with poor prognosis in systemic DLBCL161718. Therefore, we also assessed the diagnostic value of CSF IL-8 and TNF-α in PCNSL patients.…”

mentioning

confidence: 99%

Cerebrospinal Fluid IL-10 and IL-10/IL-6 as Accurate Diagnostic Biomarkers for Primary Central Nervous System Large B-cell Lymphoma

Song

Zhang

et al. 2016

Sci Rep

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Early diagnosis of primary central nervous system lymphoma (PCNSL) represents a challenge, and cerebrospinal fluid (CSF) cytokines may be diagnostic biomarkers for PCNSL. We used an electrochemiluminescence immunoassay to measure interleukin (IL)-10, IL-6, IL-8 and tumor necrosis factor α (TNF-α) in the CSF of 22 B cell PCNSL patients and 80 patients with other CNS diseases. CSF IL-10 was significantly higher in PCNSL patients than in the control group (median 74.7 pg/ml vs < 5.0 pg/ml, P < 0.000). Using a CSF IL-10 cutoff value of 8.2 pg/ml, the diagnostic sensitivity and specificity were 95.5% and 96.1%, respectively (AUC, 0.957; 95% CI, 0.901–1.000). For a CSF IL-10/IL-6 cutoff value of 0.72, the sensitivity was 95.5%, and the specificity was 100.0% (AUC, 0.976; 95% CI, 0.929–1.000). An increased CSF IL-10 level at diagnosis and post-treatment was associated with poor Progression free survival (PFS) for patients with PCNSL (P = 0.0181 and P = 0.0002, respectively). A low diagnostic value for PCNSL was found with CSF IL-8 or TNF-α. In conclusion, increased CSF IL-10 was a reliable diagnostic biomarker for large B cell PCNSL, and an IL-10/IL-6 ratio facilitates differentiation from other conditions, especially a CNS infection.

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“…However, we found a significant positive correlation between CD68 TAM number and β 2 -microglobulin. The IPI was strongly correlated with β 2 -microglobulin in DLBCL [39]. Diffuse large B-cell lymphomas display aberrant β 2 -microglobulin in protein expression, and the defects in β 2 -microglobulin expression are associated with loss of cell surface HLA-I expression.…”

Section: Disscussionmentioning

confidence: 86%

Toll-like receptor 4–induced inflammatory responses contribute to the tumor-associated macrophages formation and infiltration in patients with diffuse large B-cell lymphoma

Wang

Zhang

et al. 2015

Annals of Diagnostic Pathology

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Serum IL-6, IL-8, IL-10 and Beta₂-Microglobulin in Association with International Prognostic Index in Diffuse Large B Cell Lymphoma

Abstract: Our data imply that interleukins and beta2-microglobulin evaluation should be used in association with the International Prognostic Index to define prognostic subgroups in diffuse large B-cell lymphoma patients.

Cited by 23 publications

References 34 publications

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Cerebrospinal Fluid IL-10 and IL-10/IL-6 as Accurate Diagnostic Biomarkers for Primary Central Nervous System Large B-cell Lymphoma

Toll-like receptor 4–induced inflammatory responses contribute to the tumor-associated macrophages formation and infiltration in patients with diffuse large B-cell lymphoma

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Serum IL-6, IL-8, IL-10 and Beta2-Microglobulin in Association with International Prognostic Index in Diffuse Large B Cell Lymphoma

Abstract: Our data imply that interleukins and beta2-microglobulin evaluation should be used in association with the International Prognostic Index to define prognostic subgroups in diffuse large B-cell lymphoma patients.

Cited by 23 publications

References 34 publications

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Cerebrospinal Fluid IL-10 and IL-10/IL-6 as Accurate Diagnostic Biomarkers for Primary Central Nervous System Large B-cell Lymphoma

Toll-like receptor 4–induced inflammatory responses contribute to the tumor-associated macrophages formation and infiltration in patients with diffuse large B-cell lymphoma

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Product

Resources

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Serum IL-6, IL-8, IL-10 and Beta₂-Microglobulin in Association with International Prognostic Index in Diffuse Large B Cell Lymphoma