The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with γ-radiation-induced T-cell lymphoblastic lymphomas

Santos, Javíer; González-Sánchez, Laura; Villa‐Morales, María; Ors, I.; López-Nieva, Pilar; Vaquero, Concepción; Gonzalez-Gugel, Elena; Fernández-Navarro, Pablo; Am, Roncero; Jl, Guénet; Montagutelli, Xavier; Fernández‐Piqueras, José

doi:10.1038/onc.2010.280

Cited by 11 publications

(9 citation statements)

References 47 publications

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“…The remaining three genes, S100A9, FABP4 and HLA-DMA , are involved in inflammatory secretions by T cells or macrophages and peptide exchanges (24–26) and were unique for single-dose treatment. One gene, PDL-1 (CD274), which was down-regulated by twofold, is an inhibitor of T-cell receptor signaling (27). To better evaluate the immune response gene expression changes specific for each radiation protocol, the specific genes were mapped to the functional networks in the IPA database and ranked by score.…”

Section: Resultsmentioning

confidence: 99%

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Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

et al. 2014

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To understand the impact of clinically relevant radiation therapy (RT) on tumor immune gene expression and to utilize the changes that occur during treatment to improve cancer treatment outcome, we examined how immune response genes are modulated in prostate cancer cells of varying p53 status. LNCaP (p53 wild-type), PC3 (p53 null) and DU145 (p53 mutant) cells received a 10 Gy single dose or 1 Gy × 10 multifractionated radiation dose to simulate hypofractionated and conventionally fractionated prostate radiotherapy. Total RNA was isolated 24 h after multi-fractionated radiation treatment and single-dose treatments and subjected to microarray analysis and later validated by RT-PCR. RT-PCR was utilized to identify total-dose inflection points for significantly upregulated genes in response to multifractionated radiation therapy. Radiation-induced damage-associated molecular pattern molecules (DAMPs) and cytokine analyses were performed using bioluminescence and ELISA. Multifractionated doses activated immune response genes more robustly than single-dose treatment, with a relatively larger number of immune genes upregulated in PC3 compared to DU145 and LNCaP cells. The inflection point of multifractionated radiation-induced immune genes in PC3 cells was observed in the range of 8–10 Gy total radiation dose. Although both multifractionated and single-dose radiation-induced proinflammatory DAMPs and positively modulated the cytokine environment, the changes were of higher magnitude with multifractionated therapy. The findings of this study together with the gene expression data suggest that cells subjected to multifractionated radiation treatment would promote productive immune cell–tumor cell interactions.

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Section: Resultsmentioning

confidence: 99%

“…Whereas PDL1, an inhibitor of T-cell receptor signaling (27), was upregulated, which indicated that both activation as well as inactivation of immune response exist in multifractionated radiation treatment. Interestingly, PDL1 was downregulated to single-dose radiation treatment in PC3 cells.…”

Section: Resultsmentioning

confidence: 99%

Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

et al. 2014

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“…At present, current thymus literature suggests that crude enzymatic preparations of collagenase are still in wide use for the isolation and study of TSC phenotype and function (Bonfanti et al, 2010;Cheng et al, 2010;Corbeaux et al, 2010;Goldberg et al, 2010;Kvell et al, 2010;Osada et al, 2010;Santos et al, 2010;Sun et al, 2010;McLelland et al, 2011;Rode and Boehm, 2012). Here, we directly compare traditional preparations of collagenase with the latest panel of Liberase enzymes for their ability to effectively isolate viable TSC, characterize TEC and subsets thereof, and for total TEC RNA obtained from pooled thymic digests to facilitate downstream molecular analysis.…”

Section: Introductionmentioning

confidence: 98%

Purified enzymes improve isolation and characterization of the adult thymic epithelium

Seach

Wong

Hammett

et al. 2012

Journal of Immunological Methods

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“…Programmed death-ligand 1 (PD-L1), also termed as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is widely reported across a range of malignant tumors, 6,7 including breast cancer, 8 T-cell lymphoblastic lymphomas, 9 non-small cell lung cancer, 10,11 primary central nervous system lymphomas, 12 non-clear-cell renal cell carcinoma, 13 gastrointestinal stromal tumors, 14 metastatic bladder cancer, 15 etc. PD-L1 is a transmembrane protein that is supposed to play a vital role in blocking the cancer immunity cycle during particular events such as tumorigenesis, pregnancy, autoimmune disease, and other disease states.…”

Section: Introductionmentioning

confidence: 99%

“…In malignant tumors, patients who have over-expression of PD-L1 in their tumors usually live a relatively shorter survival than those with relatively lower PD-L1 expression 10,16,17 . Thus, therapies targeting PD1/PD-L1 have been increasing greatly in the past decade, 18,19 aiming at restoring the immune activity in tumors, but with inconsistent responding rate across different tumors 9,20 …”

Section: Introductionmentioning

confidence: 99%

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

Wang¹,

Zhang²,

et al. 2016

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Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice.Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available. R language was used as the main tool for statistical analysis and graphical work.Results: PD-L1 expression was found to be positively correlated with WHO grade of glioma. PD-L1 seemed to express more in mesenchymal subtype according to TCGA transcriptional classification scheme and may contribute as a potential marker for mesenchymal subtype in glioblastoma. Pearson correlation test indicated that PD-L1 showed robust correlation with PD1, PD-L2, and CD80 in CGGA dataset. Subsequent gene ontology analysis based on significantly correlated genes of PD-L1 revealed that PD-L1 seemed to be profoundly associated with T cell activation. To further investigate the relationship between PD-L1 expression and immune response, we selected a series of immune signatures, which were then transformed into metagenes, and found that PD-L1 expression was particularly paralleled with T-cells and macrophages-related immune response instead of B cell linage-related immune response. In line with the corresponding biological process, PD-L1 exhibited predictive value for glioma patients: Higher PD-L1 indicated significantly shorter survival, especially in glioblastoma.Conclusion: PD-L1 is upregulated in glioblastoma, and is synergistic with other check point members. Moreover, PD-L1 is significantly associated with T-cell activation and macrophage-related immune response and predicts much worse survival for patients, warranting clinical trials of PD1/PD-L1 checkpoint inhibitors for potential glioma treatment.

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The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with γ-radiation-induced T-cell lymphoblastic lymphomas

Cited by 11 publications

References 47 publications

Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

Purified enzymes improve isolation and characterization of the adult thymic epithelium

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

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