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Gene expression profiles of PD-L1 SP142 expression in triple-negative breast cancer

ABSTRACT: Gene expression profiles of PD-L1 SP142 expression in triple-negative breast cancer

PROVIDER: PRJNA660764 | ENA |

REPOSITORIES: ENA

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Gene expression profiles of PD-L1 SP142 expression in triple-negative breast cancer

Project description:The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides where PD-L1-positivity for an individual sample was defined as ≥1% of tumor-infiltrating immune cells as having PD-L1 expression. The PD-L1-positive gene signature consisted of 94 immune-related genes. The PD-L1-positive signature was predictive of pathologic complete response and survival outcome in multiple TNBC cohorts. In other malignancies treated with ICIs, the PD-L1-positive signature was associated with response and improved survival.

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Expression data in PD-L1 positive and PD-L1 negative human melanoma samples

Project description:Blocking the PD-1/PD-L1 immunosuppressive pathway has shown promise in the treatment of certain cancers including melanoma. This study investigates differences in the gene expression profiles of human melanomas that do or do not display the immunosuppressive protein PD-L1. Further understanding of genes expressed within the tumor microenvironment of PD-L1+ tumors may lead to improved rationally designed treatments. Gene expression profiling was performed on total RNA extracted by laser capture microdissection from 11 archived formalin-fixed paraffin-embedded (FFPE) melanoma specimens, 5 of which were PD-L1 positive and 6 PD-L1 negative. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: Janis M. Taube, Geoffrey D. Young, Tracee L. McMiller, Shuming Chen, January T. Salas, Theresa S. Pritchard, Haiying Xu, Alan K. Meeker, Jinshui Fan, Chris Cheadle, Alan E. Berger, Drew M. Pardoll, and Suzanne L. Topalian, Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade, Clin Cancer Res 2015, in press.

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The Association of Genomic Lesions and PD-1/PD-L1 Expression in Resected Triple Negative Breast Cancers

Project description:We used DNA content-based flow cytometry to distinguish and isolate nuclei of clonal tumor populations from resected triple negative breast cancer tissues. We then interrogated each sorted tumor population with whole genome aCGH and next generation sequencing (NGS). The genomic data was correlated with IHC staining for PD-1 and PD-L1.

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PD-L1 Mediated Immune Evasion in Triple Negative Breast Cancer Is Linked to the Loss of ZNF652

Project description:The intrinsic regulation of PD-L1 expression remains unclear. Here we report that ZNF652 is a potent transcription repressor of PD-L1. ZNF652 frequently loses heterozygosity (LOH) in various cancers. Higher LOH rate and lack of estrogen-inducible transcription lead to suppressed expression of ZNF652 in triple-negative breast cancer (TNBC). Mechanistically, ZNF652 is physically associated with the NuRD transcription corepressor complex to repress a cohort of genes, including PD-L1. Overexpression of ZNF652 inhibits PD-L1 transcription, whereas depletion of ZNF652 upregulates PD-L1. Loss of ZNF652 in TNBC unleashes PD-L1-mediated immune evasion both in vitro and in vivo. Significantly, ZNF652 expression is progressively lost during breast cancer progression, and low ZNF652 level is correlated with elevated PD-L1 expression, less infiltrated CD8+ T cells, and poor prognosis in TNBC. Our study provides novel insights into PD-L1 regulation, and supports the pursuit of ZNF652 as a potential biomarker and drug target for breast cancer immunotherapy.

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Project description:The Association of Genomic Lesions and PD-1/PD-L1 Expression in Resected Triple Negative Breast Cancers

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Project description:PD-L1 blockade-induced temporal single cell dynamics in triple negative breast cancer

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Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma.

Project description:LC-MS/MS targeted files submitted as support material for the paper: Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma.

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