PD-L1-Mediated Immunosuppression in Glioblastoma Is Associated With the Infiltration and M2-Polarization of Tumor-Associated Macrophages

Zhu, Zhiyuan; Zhang, Hongbo; Chen, Baodong; Liu, Xing; Zhang, Shizhong; Zong, Zhitao; Gao, Mengqi

doi:10.3389/fimmu.2020.588552

Cited by 102 publications

(78 citation statements)

References 60 publications

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“…Chemokines involved in immunosuppressive process induced by Macrophages and Tregs (IL-4, IL-10, IL-13, TGF-β) were also significantly upregulated in high-risk group ( P < .001)( Figure 6g ). 33–35 These data suggest high-risk patients exhibit inertia in antitumor immunities, which might contribute to their poor prognosis.…”

Section: Resultsmentioning

confidence: 95%

“… 50 They are shaped by chemokines such as IL-4, IL10 and IL-13 to impede anti-tumor immunity. 33 , 34 In the present study, CIBERSORT and IMMUNECELL AI were used to infer immune cell infiltrations in ccRCC, Tregs and TAMs are both upregulated in high-risk tumors deduced by two algorithms. We further proved this result by mIHC detection of FOXP3+ Tregs and CD68+ CD163+ Macrophages in the TMA.…”

Section: Discussionmentioning

confidence: 99%

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Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

Yin

Wang

et al. 2021

OncoImmunology

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Clear cell renal cell carcinoma (ccRCC) is the most common kidney malignancy characterized by a poor prognosis. The treatment efficacy of immune checkpoint inhibitors (ICIs) also varies widely in advanced ccRCC. We aim to construct a robust gene signature to improve the prognostic discrimination and prediction of ICIs for ccRCC patients. In this study, adopting differentially expressed genes from seven ccRCC datasets in GEO (Gene Expression Omnibus), a novel signature (FOXM1&TOP2A) was constructed in TCGA (The Cancer Genome Atlas) database by LASSO and Cox regression. Survival and time-dependent ROC analysis revealed the strong predictive ability of our signature in discovery set, two online validation sets and one tissue microarray (TMA) from our institution. High-risk group based on the signature comprises more high-grade (G3&G4) and advanced pathologic stage (stageIII/IV) tumors and presents hyperactivation of cell cycle process according to the functional analysis. Meanwhile, high-risk tumors demonstrate an immunosuppressive phenotype with more infiltrations of regulatory T cells (Tregs), macrophages and high expressions of genes negatively regulating anti-tumor immunity. Low-risk tumors have an improved response to anti-PD-1 therapy and the predictive ability of our signature is better than other recognized biomarkers in ccRCC. A nomogram containing this signature showed a high predictive accuracy with AUCs of 0.90 and 0.84 at 3 and 5 years. Overall, this robust signature could predict prognosis, evaluate immune microenvironment and response to anti-PD-1 therapy in ccRCC, which is very promising in clinical promotion.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

Yin

Wang

et al. 2021

OncoImmunology

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“…[ 16 ]. Zhu and coworkers [ 17 ] analyzed gene expression data and clinical information of about 1000 glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, finding a positive correlation of tumor PD-L1 expression with M2 polarization of infiltrating macrophages (M2-TAMs) along with an unfavorable prognostic significance of PD-L1 expression on GBM.…”

Section: Introductionmentioning

confidence: 99%

Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management

Giordano

Sabatino²,

Romano

et al. 2021

IJMS

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Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s− had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.

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“… 9–11 PD-L1-mediated immunosuppression in GBM is associated with M2 macrophage polarization and poor survival. 12 , 13 The PD-L1 status of a tumor was reported to be correlated to the outcome of PD-L1 blockade, and responses were significantly higher in PD-L1-expressing tumors than in PD-L1-nonexpressing tumors. 14 Thus, the PD-L1 level in GBM is considered a major predictive marker of PD-1/PD-L1 antibody response.…”

Section: Introductionmentioning

confidence: 99%

Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide

Lee¹,

Lin²,

Kuo³

et al. 2021

IJN

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Purpose Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI. Methods The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis. Results PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively. Conclusion This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.

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PD-L1-Mediated Immunosuppression in Glioblastoma Is Associated With the Infiltration and M2-Polarization of Tumor-Associated Macrophages

Cited by 102 publications

References 60 publications

Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management

Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide

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