A Quantitative Digital Analysis of Tissue Immune Components Reveals an Immunosuppressive and Anergic Immune Response with Relevant Prognostic Significance in Glioblastoma

Gastearena, Miguel Ángel Idoate; López-Janeiro, Álvaro; Aznarez, Arturo Lecumberri; Arana-Iñiguez, Iñigo; Guillén-Grima, Francisco

doi:10.3390/biomedicines10071753

Cited by 6 publications

(5 citation statements)

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“…In addition, lymphocyte infiltration in tumors is related to the superior prognosis of patients with cancer ( 31 ). Moreover, in a recent quantitative digital analysis, the researchers reported that high expressions of CD8+ and CD163+ cells were significantly connected with inferior survival in patients with GBM ( 32 ). According to their observations, a direct correlation was found between CD163 values and CD8 or PDL1/PD1 infiltration in patients with GBM ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in a recent quantitative digital analysis, the researchers reported that high expressions of CD8+ and CD163+ cells were significantly connected with inferior survival in patients with GBM ( 32 ). According to their observations, a direct correlation was found between CD163 values and CD8 or PDL1/PD1 infiltration in patients with GBM ( 32 ). Therefore, the high SII value can be adopted for predicting the dismal prognosis of glioma cases.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic role of the pretreatment systemic immune-inflammation index in patients with glioma: A meta-analysis

Zhang

Ni²

2023

Front. Neurol.

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BackgroundThe systemic immune-inflammation index (SII) has been recognized as the indicator that reflects the status of immune responses. The SII is related to the prognostic outcome of many malignancies, whereas its role in gliomas is controversial. For patients with glioma, we, therefore, conducted a meta-analysis to determine if the SII has a prognostic value.MethodsStudies relevant to this topic were searched from 16 October 2022 in several databases. In patients with glioma, the relation of the SII level with the patient prognosis was analyzed based on hazard ratios (HRs) as well as corresponding 95% confidence intervals (CIs). Moreover, subgroup analysis was conducted to examine a possible heterogeneity source.ResultsThere were eight articles involving 1,426 cases enrolled in the present meta-analysis. The increased SII level predicted the dismal overall survival (OS) (HR = 1.81, 95% CI = 1.55–2.12, p < 0.001) of glioma cases. Furthermore, an increased SII level also predicted the prognosis of progression-free survival (PFS) (HR = 1.87, 95% CI = 1.44–2.43, p < 0.001) in gliomas. An increased SII was significantly associated with a Ki-67 index of ≥30% (OR = 1.72, 95% CI = 1.10–2.69, p = 0.017). However, a high SII was not correlated with gender (OR = 1.05, 95% CI = 0.78–1.41, p = 0.734), KPS score (OR = 0.64, 95% CI = 0.17–2.37, p = 0.505), or symptom duration (OR 1.22, 95% CI 0.37–4.06, p = 0.745).ConclusionThere was a significant relation between an increased SII level with poor OS and the PFS of glioma cases. Moreover, patients with glioma with a high SII value have a positive relationship with a Ki-67 of ≥30%.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic role of the pretreatment systemic immune-inflammation index in patients with glioma: A meta-analysis

Zhang

Ni²

2023

Front. Neurol.

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“…The high expression of TAMs indicated a short survival time in patients with Gb. In the study of Idoate Gastearena et al ( 35 ), the median value of CD163+ TAMs was 10.48%. Based on this cutoff value, there was a negative correlation between CD163+ TAM infiltration and OS.…”

Section: Discussionmentioning

confidence: 93%

Correlation of tumor-associated macrophage infiltration in glioblastoma with magnetic resonance imaging characteristics: a retrospective cross-sectional study

Zhou,

Xue,

Man

et al. 2023

Quant Imaging Med Surg

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Background Glioblastoma (Gb) is the most common primary malignant tumor of brain with poor prognosis. Immune cells are the main factors affecting the prognosis of Gb, tumor-associated macrophages (TAMs) are the predominant infiltrating immune cell population in the immune microenvironment of Gb. Analyzing the relationship between magnetic resonance imaging (MRI) features and TAMs of Gb, and using imaging features to characterize the infiltration level of TAMs in tumor tissue may provide indicators for clinical decision-making and prognosis evaluation of Gb. Methods Data from 140 in patients with isocitrate dehydrogenase (IDH) wild-type Gb diagnosed via histopathology and molecular diagnosis in the Second Hospital of Lanzhou University from January 2018 to April 2022 were collected in this retrospective, cross-sectional study. MRI images were reviewed for lesion location, cyst, necrosis, hemorrhage, contrast-enhanced T1-weighted MRI signal intensity, average apparent diffusion coefficient (ADCmean), and minimum apparent diffusion coefficient (ADCmin). Immunohistochemical staining with anti-CD163 and anti-CD68 antibodies was employed for macrophage detection. The positive cell percentage was estimated in 9 microscopic fields at 400× magnification per whole-slide image with ImageJ software (National Institutes of Health). Additionally, the relationship between MRI features, molecular, states and the positive CD68 and CD163 expression was analyzed. Results Our study discovered that the mean or median values of CD68+ and CD163+ TAMs were 7.39% and 14.98%, respectively. There was an obvious correlation between CD163+ TAMs and CD68+ TAMs (r=0.497; P=0.000). CD68+ and CD163+ macrophage infiltration correlated with age at diagnosis in patients with Gb (CD68+: r=0.230, P=0.006; CD163+: r=0.172, P=0.042). The levels of Gb TAM infiltration in different tumor locations varied, with the temporal lobe having the highest CD163+ macrophage and CD68+ macrophage infiltration (18.58% and 9.46%, respectively). CD163+ macrophage infiltration was positively correlated with ADCmean (r=0.208; P=0.014). The infiltration of CD68+ macrophages differed significantly between groups with varying degrees of tumor enhancement (H =4.228; P=0.017). There was a significant difference in CD68+ TAMs and CD163+ TAMs between the wild-type and mutant-type telomerase reverse transcriptase (TERT) types (P=0.004 and P=0.031, respectively). Conclusions Age, location of the tumor, degree of tumor enhancement, ADC value, and TERT mutation status were associated with macrophage infiltration. These findings may serve as an effective tool for characterizing the tumor microenvironment in patients with Gb.

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“…Reversal of this sequestering through immunotherapy has shown to be an effective adjunctive therapy ( 21 ). Additionally, increased expression of CD8+ cells and CD163+ cells have demonstrated to be correlated with worse survival and prognosis due to lymphocyte immunosuppression ( 32 , 39 ). Additionally, the GBM microenvironment includes glioma stem-like cells (GSCs) which evade immune therapies through multiple mechanisms including but not limited to the down regulation of MHC class I molecules, increasing Treg cells within the microenvironment, increasing TAM-produced TGF-β, and resulting down regulation of MHC II ( 40 ).…”

Section: Intrinsic Factors Of Resistance In Gbmmentioning

confidence: 99%

Barriers to overcoming immunotherapy resistance in glioblastoma

et al. 2023

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Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

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A Quantitative Digital Analysis of Tissue Immune Components Reveals an Immunosuppressive and Anergic Immune Response with Relevant Prognostic Significance in Glioblastoma

Cited by 6 publications

References 58 publications

Prognostic role of the pretreatment systemic immune-inflammation index in patients with glioma: A meta-analysis

Prognostic role of the pretreatment systemic immune-inflammation index in patients with glioma: A meta-analysis

Correlation of tumor-associated macrophage infiltration in glioblastoma with magnetic resonance imaging characteristics: a retrospective cross-sectional study

Barriers to overcoming immunotherapy resistance in glioblastoma

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