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Transcriptomic analysis of PD-L1 positive and negative hot lung adenocarcinomas identifies a different molecular immunogenic landscape

ABSTRACT: Transcriptomic analysis of PD-L1 positive and negative hot lung adenocarcinomas identifies a different molecular immunogenic landscape

PROVIDER: PRJNA747927 | ENA |

REPOSITORIES: ENA

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Transcriptomic analysis of PD-L1 positive and negative hot lung adenocarcinomas identifies a different molecular immunogenic landscape

Project description:Lung cancer is a major global health problem, as it is the leading cause of cancer- related deaths worldwide. Non-small-cell lung cancer (NSCLC), the most common form, is a heterogeneous disease with adenocarcinoma and squamous cell carcinoma being the predominant subtypes. Immune-inhibiting interaction of Programmed cell death-ligand 1 (PD-L1) with programmed cell death-protein 1 (PD-1) causes checkpoint mediated immune evasion and is, accordingly, an important therapeutic target in cancer. In NSCLC, improved understanding of PD-1/PD-L1 checkpoint blockade-responsive biology is warranted. We aimed to identify the landscape of immune cell infiltration in primary lung adeno- carcinoma (LUAD) in the context of tumor PD-L1 expression and the extent of immune infiltration (“hot” vs. “cold” phenotype). Therefore, the study comprises LUAD cases (n=138) with “hot” and “cold” tumor immune phenotype and positive and negative tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4 and CD8 and further analyzed on transcriptomic level by Nanostring nCouter Pan Cancer Immune Profiling Panel. We detected significantly differentially expressed genes associated with PD-L1 positive and “hot” versus PD-L1 negative and “cold” phenotype. The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification.

2021-09-27 | GSE180347 | GEO

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.

2015-05-01 | E-GEOD-65041 | biostudies-arrayexpress

PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy [scRNA-seq]

Project description:Dendritic cells (DCs) express high levels of PD-L1 in the tumor microenvironment and draining lymph nodes. Here, we explore the roles of PD-L1 signaling during immunogenic chemotherapy. DC-conditional PD-L1 knockout mice were inoculated with MC38-OVA tumors and treated with doxorubicin. T cells were isolated from draining lymph node for single cell RNA sequencing.

2024-09-23 | GSE223509 | GEO

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

2015-05-01 | GSE65041 | GEO

PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy

Project description:PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy

| PRJNA876931 | ENA

PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy

Project description:Dendritic cells (DCs) express high levels of PD-L1 in the tumor microenvironment. However, the physiological functions of PD-L1 on DCs remain incompletely understood. Here, we explored the roles of PD-L1 signaling in dendritic cells. PD-L1 was knocked out in DC2.4 cells and transcriptional profiles were analyzed.

2024-09-23 | GSE212711 | GEO

PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy [scRNA-seq]

Project description:PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy [scRNA-seq]

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Gene-expression profiles of PD-L1-affected CD8+ T cells

Project description:Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Tumor cell lysis by CTLs was attenuated when PD-L1 on tumor cells was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. Gene expression profile of mouse CTLs caused by PD-L1-overexpressing ovarian cancer was related to human CTLs exhaustion. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in OT-1 mouse CD8+ T cells that were co-incubated with OVA peptide-loaded ID8 mouse ovarian cancer cell lines. CTLs from 4 mice were devided into 2 groups, and co-incubated with PD-L1-overexpressed ID8 or PD-L1-depleted ID8.

2012-07-09 | E-GEOD-39205 | biostudies-arrayexpress

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.

2021-07-14 | GSE157284 | GEO