Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272776 | ENA |
REPOSITORIES: ENA
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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
Project description:PD-L1 is a ligand for the inhibitory PD1 receptor on T cells and its expression in some cancers inhibits anti-cancer immune response. In melanoma, PD-L1 expression is induced in response to immune stimuli but in a proportion of melanomas it is constitutively expressed. Factors that drive constitutive expression of PD-L1 are unknown. Here we performed genome-scale methylation analysis of six cell lines that constitutively express PD-L1 (PD-L1 positive, referred to as PD-L1CON) and six cell lines that only express PD-L1 after treatment with IFN- (PD-L1 negative, referred to as PD-L1IND)
2018-05-24 | GSE107621 | GEO
Project description:PD-L1 is a ligand for the inhibitory PD1 receptor on T cells and its expression in some cancers inhibits anti-cancer immune response. In melanoma, PD-L1 expression is induced in response to immune stimuli but in a proportion of melanomas it is constitutively expressed. Factors that drive constitutive expression of PD-L1 are unknown. Here we performed RNA-Seq analysis of six cell lines that constitutively express PD-L1 (PD-L1 positive, referred to as PD-L1CON) and six cell lines that only express PD-L1 after treatment with IFN- (PD-L1 negative, referred to as PD-L1IND)
2018-05-24 | GSE107620 | GEO
Project description:Expression data from Helicobacter positive and negative human gastritis samples
| PRJNA95379 | ENA
Project description:Purpose: Use RNA-seq strategy to characterize the PD-L1 correlated genes in sorted PD-L1 negative and positive doxorubicin-induced senescent and normal human foreskin fibroblasts HCA2 cells to identify the upstream transcriptional network for regulating heterogeneous PD-L1 expression in senescent cells. Methods: Early passaged normal HCA2 cells and senescent HCA2 cells induced by 24 hours of 100 nM doxorubicin treatment were utilized for the preparation of bulk RNA-seq libraries. Among the senescent cells, PD-L1 positive and negative cells were separated by FACSorting.
2022-08-27 | GSE198396 | GEO
Project description:Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. 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. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. 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 human ovarian cancer tissue from ascites-cytology-positive or -negative patients.
2012-07-09 | E-GEOD-39204 | biostudies-arrayexpress
Project description:Disrupting PD-1/PD-L1 interaction rejuvenates antitumor immunity. Clinical successes by blocking PD-1/PD-L1 binding have grown across wide-ranging cancer histologies, but innate therapy resistance is evident in the majority of treated patients1. Cancer cells can express robust surface levels of PD-L1 to tolerize tumor-specific T cells, but regulation of PD-L1 protein levels in the cancer cell is poorly understood. Quasi-mesenchymal tumor cells up-regulate PD-L1/L2 and induce an immune-suppressive microenvironment, including expansion of M2-like macrophages and regulatory T cells and exclusion of CD8+ T-cell infiltration2. Targeted therapy, including MAPK inhibitor therapy in melanoma, leads to quasi-mesenchymal transitions and resistance3, and both MAPK inhibitor treatment and mesenchymal signatures are associated with innate anti-PD-1 resistance4,5. Here we identify ITCH as an E3 ligase that downregulates tumor cell-surface PD-L1/L2 in PD-L1/L2-high cancer cells, including MAPK inhibitor-resistant melanoma, and suppresses acquired MAPK inhibitor resistance in and only in immune-competent mice. ITCH interacts with and poly-ubiquitinates PD-L1/L2, and ITCH deficiency increases cell-surface PD-L1/L2 expression and reduces T cell activation. Mouse melanoma tumors grow faster with Itch knockdown only in syngeneic hosts but not in immune-deficient mice. MAPK inhibitor therapy induces tumor cell-surface PD-L1 expression in murine melanoma, recapitulating the responses of clinical melanoma3, and this induction is more robust with Itch knockdown. Notably, suppression of ITCH expression first elicits a shift toward an immune-suppressive microenvironment and then accelerates resistance development. These findings collectively identify ITCH as a critical negative regulator of PD-L1 tumor cell-surface expression and provide insights into previously unexplained role of PD-L1 in adaptive resistance to therapy.
2022-03-31 | MSV000089180 | MassIVE
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
Project description:PD-L1 suppresses host immunity and promotes tumor growth. We investigated how IFN-? regulates PD-L1 in the ovarian cancer microenvironment. In clinical samples, the number of stromal CTLs in peritoneally disseminated tumors was correlated with PD-L1 expression on the tumor cells, and the lymphocyte number was significantly related to the IFN-? signature score. In mouse models, PD-L1 was induced in peritoneal disseminated tumors, where lymphocytes were prominent, but not in subcutaneous tumors. Depleting IFNGR1 resulted in lower PD-L1 expression and longer survival in peritoneal dissemination model. Injection of IFN-? into subcutaneous tumors increased PD-L1 expression and tumor size, and PD-L1 depletion abrogated tumor growth. These data suggest that IFN-? works as a tumor progressor through PD-L1 induction. The source of IFN-? in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-? and expression microarray analysis was performed, and probes showing significantly higher values in IFN-?-added group were termed “IFN-? signature genes (295 probes)”. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-? signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-? in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-?-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment. Genome-wide transcriptional changes in human ovarian cancer tissue were observed in different tumor immunological microenvironment.
2014-03-04 | E-GEOD-55512 | biostudies-arrayexpress
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO