Th1/Th2 cytokine imbalance in meningioma, anaplastic astrocytoma and glioblastoma multiforme patients

Kumar, Rajesh; Kamdar, Dev; Madden, Leigh A.; Hills, Caitlin; Crooks, Daniel; O’Brien, Daniel R.; Greenman, J.

doi:10.3892/or.15.6.1513

Cited by 41 publications

(41 citation statements)

References 18 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, serum IL-10 level has been previously described as significantly increased in high-grade glioma patients compared with non-tumor control patients (13). Similarly, IL-10 was identified in our study as a serum biomarker that accurately classified GBM patients from controls.…”

Section: Discussionsupporting

confidence: 48%

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

Gowda

et al. 2012

Int J Oncol

View full text Add to dashboard Cite

Abstract. Analyzing molecular biomarkers using blood is an important approach for clinical assessment of malignant glioma. We investigated a molecular proteomic biomarkerbased approach for glioblastoma using patients' blood samples. The expression levels of a list of candidate proteins were quantified in plasma and serum samples from two different cohorts of patients with malignant glioma and normal controls. The biological function was studied for one of the identified markers. Additionally, the prognostic significance of protein marker expression was measured by survival analysis. As a result, protein biomarkers associated with malignant glioma were identified from the blood specimens and five of the protein biomarkers were common to both cohorts. Immunohistochemical analysis demonstrated that many of the protein biomarkers identified in peripheral blood specimens were expressed in malignant gliomas. Staining levels for one of the biomarkers, MIP-1α, was found to correlate with WHO grade among invasive gliomas, and we demonstrate that MIP-1α promotes human glioblastoma cell proliferation and migration. Additionally, four prognostic protein biomarkers were identified. In conclusion, we demonstrate that both peripheral blood plasma and serum specimens are highly valuable and complementary to each other in the quest for protein biomarkers of malignant glioma. Sets of novel protein biomarkers were identified that may aid in the diagnosis and prognosis of patients with malignant glioma.

show abstract

Section: Discussionsupporting

confidence: 48%

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

Gowda

et al. 2012

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…In a cohort of primary brain tumors, an imbalance in the systemic IL-12/IL-10 balance as hallmarks of Th1/Th2 cytokine production has been shown. This Th1/Th2 cytokine imbalance in patients with brain tumors is similar to that observed in studies on several other tumor types (Kumar et al, 2006). Currently, it is not known whether the lack of Th1 type response in these tumors is accompanied by elevation in Th17 type of response or not.…”

Section: Introductionsupporting

confidence: 58%

Elevated Serum IL-17A but not IL-6 in Glioma Versus Meningioma and Schwannoma

Doroudchi

Pishe²,

Malekzadeh³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera (0.29±0.54, 0.03±0.15 and 0.16±0.68 vs. 0.00±0.00pg/ml; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls (2.34±4.35 vs. 4.67±4.32pg/ml; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

show abstract

“…Such studies could also address other questions by investigating the circulating helper T cell profile in a large number of glioblastoma patients and correlating it with, not just tumoral 10q status, the parameter analyzed in our report, but with mutations in each of the three specific 10q oncogenes, and with the subsequent development of clinical infections. If our data is elaborated upon in this manner, the fact that the majority of glioblastomas exhibit LOH 10q could explain why the majority of glioblastoma patients exhibit a circulating Th2 rather than Th1 profile, one that promotes humoral immunity against systemic infection but weakens cellular antitumor immunity [19]. Further investigation of the different effects of an oncogene mutation on antitumor cellular versus systemic humoral immunity could provide insight into both antitumor immunity and host defenses against local and systemic infection.…”

Section: Discussionmentioning

confidence: 89%

“…Of note, two-thirds of glioblastoma patients have tumor-secreted cytokines that favor a circulating Th2 profile, while 1/3 of glioblastomas secrete cytokines favoring a Th1 profile [7,8]. One study found that most glioblastoma patients have both elevated circulating levels of interleukin 10, a Th2 promoting cytokine, and reduced circulating interleukin 12, a Th1 promoting cytokine, and that the changes were independent of corticosteroid usage [19]. A similar report found that the Th1-promoting cytokines tumor necrosis factor (TNF) a and interferon (IFN) gamma were reduced in peripheral lymphocytes and glioma cell cultures compared to controls, and that the Th2 promoting cytokines interleukin 4 and interleukin 10 were elevated in peripheral lymphocytes and glioma cell cultures compared to controls [20].…”

Section: Discussionmentioning

confidence: 99%

Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q

et al. 2009

View full text Add to dashboard Cite

Introduction Chromosome 10q allelic loss commonly occurs in glioblastoma. Disruption of PTEN, one of three known 10q tumor suppressor genes, affects the immune system by increasing tumor expression of immunosuppressive protein B7-H1 and by increasing tumor release of Th2-inducing cytokines. While the former might impair antitumor cellular immunity, a consideration for immunotherapy, the latter could cause 10q-maintaining tumor patients to experience comparatively higher rates of bacterial infections, a source of morbidity and mortality in glioblastoma patients. Methods We retrospectively reviewed 58 glioblastoma patients whose tumors were designated ''normal-10q'' (n = 16) or ''LOH-10q'' (n = 42) using loss of heterozygosity (LOH) assays of microsatellite markers in constitutional/tumor DNA pairs. Records were reviewed for symptomatic, microbiologically or radiographically confirmed infections in the first 2 years after diagnosis. Results Infection occurred more frequently in ''normal-10q'' than ''LOH-10q'' patients (56% vs. 14% of patients experiencing infection; P = 0.001). ''Normal-10q'' patients more commonly developed all four infection types studied (urinary tract = 38% vs. 13%, craniotomy wound = 19% vs. 0%, pneumonia = 19% vs. 5%, sepsis = 6% vs. 3%). ''Normal10q'' and ''LOH-10q'' patients had similar survival, ages, chemotherapy treatment rates, and frequency of patients on dexamethasone 1 month after radiation therapy (P = 0.4-0.98), making these factors unlikely to explain the observed difference in infection rates. Conclusion While tumor mutations may inhibit antitumor immunity, the effects of these mutations on systemic immunity remain undetermined. We found higher infection rates after glioblastoma diagnosis in patients whose tumors maintained chromosome 10q than in patients whose tumors had allelic 10q loss. Differing effects of this genetic alteration on antitumor and systemic immunity may warrant further investigation, potentially providing insight into mechanisms of antitumor immunity and host defenses against local and systemic infections.

show abstract

Th1/Th2 cytokine imbalance in meningioma, anaplastic astrocytoma and glioblastoma multiforme patients

Cited by 41 publications

References 18 publications

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

Elevated Serum IL-17A but not IL-6 in Glioma Versus Meningioma and Schwannoma

Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q

Contact Info

Product

Resources

About