Immune phenotypes predict survival in patients with glioblastoma multiforme

Mostafa, Haouraa; Paľa, Andrej; Högel, Josef; Hlaváč, Michal; Dietrich, Elvira; Westhoff, Mike‐Andrew; Nonnenmacher, Lisa; Burster, Timo; Georgieff, Michael; Wirtz, Christian Rainer; Schneider, E. Marion

doi:10.1186/s13045-016-0272-3

Cited by 55 publications

(56 citation statements)

References 45 publications

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“…Previous studies have focused on the prognostic value of various tumor‐infiltrating cell populations in GBMs (Becht et al , 2016a; Klopfenstein et al , 2019). As an example, the association of T‐cell infiltration with patient outcome has been investigated by several research groups (Han et al , 2014; Kmiecik et al , 2013; Mostafa et al , 2016; Preusser et al , 2015) and has reached inconsistent results. This underscores the complexity of the tumor microenvironment and therefore the need for further characterization.…”

Section: Introductionmentioning

confidence: 99%

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

et al. 2020

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Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in-house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM.

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Section: Introductionmentioning

confidence: 99%

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

et al. 2020

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“…Of these 31 studies, 24 articles assessed the relationship between blood‐based inflammatory cytokines and glioma risk. Table presents the characteristics and quality evaluation of these 24 included studies.…”

Section: Resultsmentioning

confidence: 99%

“…Of these 24 studies, 10 examined IL‐6, five examined IL‐8, four examined interleukin‐17 (IL‐17), nine examined TNF‐ α , three examined transforming growth factor‐ β (TGF‐ β ), two examined CRP, three examined interleukin‐4 (IL‐4), five examined IL‐10, three examined interleukin‐12 (IL‐12), two examined interleukin‐23 (IL‐23), and four examined monocyte chemotactic protein‐1 (MCP‐1) . Among these 24 studies, serum samples from patients with glioma were collected in 22, and plasma samples were collected in the other two . Most of these studies used an enzyme‐linked immunosorbent assay (ELISA) to detect the concentrations of inflammatory cytokines, and only a few studies used other methods, such as bead array technology, fluorescence microsphere detection, xMAP, and radioimmunoassays .…”

Section: Resultsmentioning

confidence: 99%

“…24,28,29,32 Among these 24 studies, serum samples from patients with glioma were collected in 22,9,10,[24][25][26][27][28][29][30][32][33][34][35][36][37][38][39][40][41][42][43]45 and plasma samples were collected in the other two. 31,44 Most of these studies used an enzyme-linked immunosorbent assay (ELISA) to detect the concentrations of inflammatory cytokines, and only a few studies used other methods, such as bead array technology, 33 fluorescence microsphere detection, 36 xMAP, 37 and radioimmunoassays. 41,45 | 7457…”

Section: Characteristics and Quality Evaluation Of The Included Stumentioning

confidence: 99%

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Relationship between circulating inflammatory factors and glioma risk and prognosis: A meta‐analysis

et al. 2019

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Background Inflammatory factors have been considered a significant factor contributing to the development and progression of glioma. However, the relationship between circulating inflammatory factors and glioma risk as well as their prognostic values in glioma patients is still inconclusive. Here, we performed a meta‐analysis to address this issue. Methods Relevant articles were identified through PubMed, EMBASE, the Cochrane Library, Web of Science, Wanfang database, and China National Knowledge Infrastructure (CNKI) from inception to February 2019. The weighted mean differences (WMDs) or standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to describe the predictive ability of the levels of circulating inflammatory factors on glioma risk. To evaluate the prognostic values of the circulating inflammatory factors in glioma, hazard ratios (HRs) with 95% CIs were used. Results Thirty‐one studies comprising 2587 patients were included. The overall analysis showed that increased circulating interleukin‐6 (IL‐6) [SMD 0.81 (95% CI: 0.21‐1.40; P = .008)], interleukin‐8 (IL‐8) [SMD 1.01 (95% CI: 0.17‐1.84; P = .018)], interleukin‐17 (IL‐17) [SMD 1.12 (95% CI: 0.26‐1.98; P = .011)], tumor necrosis factor‐α (TNF‐α) [SMD 1.80 (95% CI: 1.03‐2.56; P = .000)], transforming growth factor‐β (TGF‐β) [SMD 10.55 (95% CI: 5.59‐15.51; P = .000)], and C‐reactive protein (CRP) [SMD 0.95 (95% CI: 0.75‐1.15; P = .000)] levels were significantly associated with glioma risk. On the other hand, our results showed that circulating IL‐6 [HR 1.10 (95% CI: 1.05‐1.16; P = .000)] and CRP [HR 2.02 (95% CI: 1.52‐2.68; P = .000)] levels were highly correlated with a poor overall survival (OS) rate in glioma patients. Conclusion Our results indicate that increased circulating IL‐6, IL‐8, IL‐17, TNF‐α, TGF‐β, and CRP levels are significantly associated with increased glioma risk. Moreover, our meta‐analysis suggests that circulating IL‐6 and CRP may serve as powerful biomarkers for a poor prognosis in glioma patients.

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“…Many advances in the understanding of cancer biology are made in the field of gene sequencing and interaction with tumor microenvironment. They aim to identify alterations of the immune system defing immune phenotypes (25,26) and cancer pathways associated with intracellular and intercellular signaling important to mediate cancer pathogenesis and progression (27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature

et al. 2018

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Abstract. Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence.

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Immune phenotypes predict survival in patients with glioblastoma multiforme

Cited by 55 publications

References 45 publications

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

Relationship between circulating inflammatory factors and glioma risk and prognosis: A meta‐analysis

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature

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