Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Role of PD-1/PD-L1 in Overshooting Osteoclastogenesis in Periprosthetic Joint Infections

ABSTRACT: Periprosthetic joint infection (PJI) is a critical complication following arthroplasty, leading to increased prosthesis failure rates post-treatment. This study explores the role of PD-1/PD-L1 signaling in osteoclastogenesis associated with PJI. Peripheral blood, bone, and bone marrow of 65 patients (20 primary osteoarthritis, 21 PJI septic explantation, 24 PJI prosthesis reimplantation) were analyzed for their bone microstructure and cell composition. Immunocytochemistry, RT-qPCR, flow cytometry, bone resorption assay, ELISA, and RNA sequencing were performed to investigate the effects of PD-1 stimulation and blockade on osteoclast formation. PD-1 positive monocytes and sPD-L1 levels were elevated in PJI. Stimulation with PD-L1 enhanced osteoclastogenesis, while PD-1 inhibitor nivolumab reversed these effects. Impact of PD-1 and nivolumab was significantly more pronounced in PJI compared to the control. Our study suggests PD-1/PD-L1 signaling plays a significant role in PJI-related osteoclastogenesis. These findings highlight the potential of PD-1 inhibitors as a novel approach to manage this challenging clinical condition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE295042 | GEO | 2025/04/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data in human renal cell carcinoma samples from patients who did or did not respond to anti-PD-1 (Nivolumab) immunotherapy

Project description:Pre-treatment tumor expression of PD-L1 has been shown to correlate with favorable clinical outcomes following PD-1 blocking therapies. However, the majority of patients with PD-L1+ tumors do not respond to treatment. With the goal of obtaining insights into the mechanisms underlying the response to anti-PD-1 targeted therapies in patients with renal cell carcinoma (RCC) with positive tumor expression of PD-L1, microarray expression data was obtained for pre-treatment tumors from patients with RCC who did or did not have a positive response to anti-PD-1 (nivolumab) therapy. Insight into these mechanisms may lead to improved rationally designed therapies, and biomarkers for selecting patients who are more likely to benefit from these treatments. Gene expression profiling was performed on total RNA extracted from 11 formalin-fixed paraffin-embedded (FFPE) RCC specimens, 4 of which were from patients who had a positive response (objective tumor regression) to the anti-PD-1 (nivolumab) immunotherapy, and 7 of which were from patients who did not have a response. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: Maria Libera Ascierto, Tracee L. McMiller, Alan E. Berger, Ludmila Danilova, Robert A. Anders, George J. Netto, Haiying Xu, Theresa S. Pritchard, Jinshui Fan, Chris Cheadle, Leslie Cope, Charles G. Drake, Drew M. Pardoll, Janis M. Taube, and Suzanne L. Topalian, The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Antiâ??PD-1 Response in Patients with Renal Cell Carcinoma, published online in Cancer Immunology Research on 4 August 2016, doi: 10.1158/2326-6066.CIR-16-0072 http://cancerimmunolres.aacrjournals.org/content/early/2016/07/28/2326-6066.CIR-16-0072.full.pdf+html

2016-08-04 | E-GEOD-67501 | biostudies-arrayexpress

Co-evolving JAK2V617F+ relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case [TCR-seq]

Project description:JAK2V617+ myeloproliferative disease has been reported to overexpress PD-L1 rationalizing therapeutic PD-1 blockade. We performed an integrated single cell analysis on samples from an exceptional responder to nivolumab to elucidate determinants of response in this patient.

2021-08-26 | GSE165851 | GEO

Co-evolving JAK2V617F+ relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case [BCR-seq]

2021-08-26 | GSE165850 | GEO

Co-evolving JAK2V617F+ relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case [CITE-seq]

2021-08-26 | GSE165822 | GEO

Co-evolving JAK2V617F+ relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case [RNA-seq]

2021-08-26 | GSE165496 | GEO

Co-evolving JAK2V617F+ relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case [ATAC-seq]

2021-08-26 | GSE165397 | 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

RNA-Seq analysis to compare myeloid cells from PD-L1-LysMCre mice with littermate Wild-type controls

Project description:Programmed death-ligand 1 (PD-L1) is predominantly expressed in the antigen-presenting cells (APCs) that are originated and abundant in bone marrow. The roles of PD-L1 in bone cell differentiation and cancer bone metastasis remain unclear. Here we show that PD-L1 antibody or PD-L1 conditional knockout in the hematopoietic or myeloid lineage suppresses osteoclast differentiation in vitro and in vivo. Bone metastases of breast cancer and melanoma are diminished by PD-L1 antibody or PD-L1 deletion in the myeloid lineage. Transcriptional profiling of bone marrow cells reveals that PD-L1 deletion in the myeloid cells up-regulates immune stimulatory genes, leading to increased macrophage M1 polarization, decreased M2 polarization, enhanced IFN? signaling, and elevated T cell recruitment and activation. All these alterations result in heightened anti-tumor immunity in the cancer microenvironment. Our findings support PD-L1 antibody as a potent therapy for bone metastasis of breast cancer and melanoma by simultaneously suppressing osteoclast and enhancing immunity.

2022-03-07 | GSE190715 | GEO

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

Expression data in human renal cell carcinoma samples from patients who did or did not respond to anti-PD-1 (Nivolumab) immunotherapy

2016-08-04 | GSE67501 | GEO