Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma

Li, Shasha; Zhang, Chaoqi; Maimela, Nomathamsanqa Resegofetse; Li, Yang; Zhang, Zhen; Yü, Ping; Huang, Lan; Zhang, Yi

doi:10.1080/2162402x.2019.1601478

Cited by 55 publications

(51 citation statements)

References 62 publications

(77 reference statements)

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“…In general, TAMs, once activated by Th2 cytokines, use many strategies to induce immunosuppression. They secrete suppressive cytokines and factors, IL-10, IL-35, and TGF-β, which contribute to the impairment of Teff proliferation and activity [ 47 ]. Alternatively, TAMs can induce exhaustion by inducing PD-L1 expression on monocytes, which bind to PD-1 on CD8+ cells.…”

Section: Influence Of the Pancreatic Tumor Microenvironment On Thementioning

confidence: 99%

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Saka

Gökalp

Piyade

et al. 2020

Cancers

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T-cell exhaustion is a phenomenon that represents the dysfunctional state of T cells in chronic infections and cancer and is closely associated with poor prognosis in many cancers. The endogenous T-cell immunity and genetically edited cell therapies (CAR-T) failed to prevent tumor immune evasion. The effector T-cell activity is perturbed by an imbalance between inhibitory and stimulatory signals causing a reprogramming in metabolism and the high levels of multiple inhibitory receptors like programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and Lymphocyte-activation gene 3 (Lag-3). Despite the efforts to neutralize inhibitory receptors by a single agent or combinatorial immune checkpoint inhibitors to boost effector function, PDAC remains unresponsive to these therapies, suggesting that multiple molecular mechanisms play a role in stimulating the exhaustion state of tumor-infiltrating T cells. Recent studies utilizing transcriptomics, mass cytometry, and epigenomics revealed a critical role of Thymocyte selection-associated high mobility group box protein (TOX) genes and TOX-associated pathways, driving T-cell exhaustion in chronic infection and cancer. Here, we will review recently defined molecular, genetic, and cellular factors that drive T-cell exhaustion in PDAC. We will also discuss the effects of available immune checkpoint inhibitors and the latest clinical trials targeting various molecular factors mediating T-cell exhaustion in PDAC.

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Section: Influence Of the Pancreatic Tumor Microenvironment On Thementioning

confidence: 99%

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Saka

Gökalp

Piyade

et al. 2020

Cancers

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“…6 The prognostic relevance of TAMs in highgrade glioma was shown to be positive, negative or absent in different studies, 7 but, generally, M2-like markers were positively associated with grade of malignancy and with poor survival in glioma. [7][8][9] Other cell types, such as myeloid-derived suppressor cells (MDSCs), have been described predominantly in the invasive margins of glioma samples, and MDSCs presence was shown to correlate with an unfavorable outcome. 3 Recent studies in glioma patients [10][11][12] have characterized gene signatures related to single immune markers and reported a correlation between myeloid marker expression and poor prognosis in GBM; however myeloid cell marker expression did not correlate with grade in glioma.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma

et al. 2020

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Glioma represents a serious health burden in terms of morbidity and mortality. The prognostic significance of the lymphoid and myeloid infiltrates in glioma is not clearly determined. Moreover, the characterization of different leukocyte subsets in the tumor microenvironment relies mainly on immunohistochemistry observations, and data about their association with prognosis are contradictory. Here, we performed acomprehensive study of both the tumor-infiltrating and circulating immune compartments of patients with high-grade glioma. Nineteen tumor biopsies and 30 PBMC samples were analyzed by RNA sequencing. Validation was performed on The Cancer Genome Atlas (TCGA) RNA sequencing data from glioma and on additional 39 tumor biopsies analyzed by flow cytometry. We identified prognostic tumor and peripheral immune signatures, which associate increased inflammation, immune infiltration and activation with shorter overall survival in high-grade glioma patients. Importantly, we confirmed our observations by flow cytometry analysis and validated the tumor-signature using the TCGA dataset. In addition, both tumor genotype and grade associated with the degree of glioma immune infiltration. Unlike in the majority of cancers, lymphocyte infiltration at the tumor site is anegative prognostic factor in glioma, suggesting the ambivalent pro-tumorigenic role of immune responses in glioma.

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“…High CD163 levels have recently been suggested to be a potential biomarker for poor prognosis in a number of solid tumours, including gliomas [44], oestrogen-receptor-positive breast cancer [45] and head and neck squamous cell carcinomas [46]. A major role of macrophages is the clearance of apoptotic cells (efferocytosis), which in the context of cancer is tumour-promoting, inducing a wound-healing immunosuppressive environment.…”

Section: Discussionmentioning

confidence: 99%

A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

Adams

Ercolano

Ferluga

et al. 2020

IJMS

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The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP™) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45+HLA-DR+CD14+CD163+) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing AKT1 E17K mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated AKT1 E17K, signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.

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Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma

Cited by 55 publications

References 62 publications

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma

A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

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