PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Programmed Cell Death 1 Receptor”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2004

Co-signaling molecules of the B7-CD28 family in positive and negative regulation of T lymphocyte responses.

Co-signaling molecules in the B7-CD28 family have been intensively studied over the past decade and have brought much excitement to the field of immune regulation. The discovery of new functions for the classical pathways CD80/CD86/CD28/CTLA-4 and the identification of novel pathways of the family, including B7-H1/B7-DC/PD-1, B7-H2/ICOS, B7-H3, B7-H4 and BTLA, are greatly broadening our understanding of the control of T cell-mediated immune responses and tolerance.

Animals↗
PubMed2005

Pathogenic roles of cardiac autoantibodies in dilated cardiomyopathy.

Whether autoimmunity could cause dilated cardiomyopathy (DCM) was disputed for more than half a century. Autoantibodies against various cardiac antigens have been found in the sera of patients with DCM but none of these autoantibodies has been shown to have a substantial role in the development of DCM. It was recently reported that the injection of autoantibodies against cardiac troponin I (cTnI) can induce DCM in normal mice. This observation showed that autoantibodies can cause DCM and put an end to the controversy. Clinical trials of immunoglobulin-adsorption therapy for DCM have already started in Germany and the results seem promising. Here, we discuss the recent findings and possibilities of immunoglobulin-adsorption therapy for this deadly disease.

Animals↗
PubMed1997

The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors.

We report the complete cDNA sequence and the genomic structure of the human PD-1 homologue. An analysis of the expression pattern of the human PD-1 gene (hPD-1) and the murine PD-1 gene (mPD-1) in developing bone marrow B-lineage cells was also undertaken. The full length hPD-1 cDNA is 2106 nucleotides long and encodes a predicted protein of 288 amino acid residues. The hPD-1 and mPD-1 genes share 70% homology at the nucleotide level and 60% homology at the amino acid level. Four potential sites for N-linked glycosylation are conserved, as are a stretch of amino acids between two cysteine residues resembling a V-set immunoglobulin domain, and another region containing a motif similar to an immunoreceptor tyrosine-based inhibitory motif. Isolation of the genomic locus of the hPD-1 gene reveals that the gene is composed of five exons located on human chromosome 2 at band q37. The 5' flanking region lacks TATA and CAAT cis-acting elements, but includes a number of potential transcription factor binding sites and a dominant transcription start site. The mPD-1 gene was preferentially expressed in pro-B cells from murine adult bone marrow. Although hPD-1 was not preferentially expressed in pro-B cells from human fetal bone marrow, treatment of isolated pro-B cells with interleukin-7 resulted in a dramatic increase in expression. These data suggest that PD-1 may play a role in B-cell differentiation during the pro-B cell stage.

Amino Acid Sequence↗
PubMed2003

Finding genes for SLE: complex interactions and complex populations.

Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We review our recent findings on the genetics of lupus, provide possible mechanisms for disease susceptibility and present some facts on the problematic of identifying susceptibility mutations for complex diseases in complex human populations.

Antigens, CD↗
PubMed1999

Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.

PD-1, a 55 kDa transmembrane protein containing an immunoreceptor tyrosine-based inhibitory motif, is induced in lymphocytes and monocytic cells following activation. Aged C57BL/6(B6)-PD-1(-/-) congenic mice spontaneously developed characteristic lupus-like proliferative arthritis and glomerulonephritis with predominant IgG3 deposition, which were markedly accelerated by introduction of a Fas mutation (lpr). Introduction of a PD-1 null mutation into the 2C-TCR (anti-H-2Ld) transgenic mice of the H-2(b/d) background resulted in the chronic and systemic graft-versus-host-like disease. Furthermore, CD8+ 2C-TCR+ PD-1(-/-) T cells exhibited markedly augmented proliferation in vitro in response to H-2d allogenic cells. Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses.

Animals↗
PubMed2026

Proteomic and Metabolomic Analysis of Immune-Related Adverse Events in Patients Treated with PD-1 Inhibitors.

As a class of immune checkpoint inhibitors (ICIs), programmed cell death protein-1 (PD-1) blockade has demonstrated remarkable efficacy in the treatment of various malignancies. However, their clinical application is constrained by the high incidence of immune-related adverse events (irAEs), which arise from nonspecific immune activation and can affect multiple organ systems, with severe cases posing life-threatening risks. This study integrated high-throughput proteomic and metabolomic analyses to systematically characterize the molecular features associated with irAEs in cancer patients receiving PD-1 inhibitor therapy. The results showed that, following the first treatment, patients who developed irAEs exhibited potential involvement of the NF-κB pathway, along with lower baseline levels of SNRPA and higher expression of CD63. Metabolomic analyses further revealed that the kynurenine/tryptophan ratio was significantly elevated in the irAE group both at baseline and post-treatment compared with patients who did not develop irAEs. In addition, significant differences in the abundance of specific lipids were observed between the two groups prior to the administration of immunotherapy. Our findings provide exploratory insights into immune and metabolic alterations associated with PD-1 blockade treatment and may help generate hypotheses for future studies on early irAE risk assessment in cancer patients undergoing PD-1 blockade therapy.

Humans↗
PubMed2002

A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.

Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.

3' Untranslated Regions↗
PubMed2005

Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4.

T cells recognizing self proteins exist without causing autoimmunity in healthy individuals. These autoreactive T cells are kept in check by peripheral tolerance. Using a model for peripheral CD8(+) T cell tolerance resulting from antigen presentation by resting dendritic cells in vivo, we show here that CD8(+) T cell tolerance operates through T cell-intrinsic mechanisms such as deletion or functional inactivation. Peripheral CD8(+) T cell tolerance depended on signaling via the costimulatory molecule PD-1, as an absence of PD-1 converted tolerance induction into priming. Blocking of the costimulatory molecule CTLA-4 resulted in impaired tolerance and enhanced the effect of the absence of PD-1, suggesting that PD-1 and CTLA-4 act synergistically. Thus PD-1 and CTLA-4 are crucial molecules for peripheral CD8(+) T cell tolerance induced by resting dendritic cells.

Animals↗
PubMed2006

Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction.

The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L2, inhibits proliferation and cytokine production mediated by antibodies to CD3 (refs. 5,6,7). Blocking the PD-1-PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8(+) T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load. During chronic HIV infection, HIV-specific CD8(+) T cells are functionally impaired, showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate. Here, we found that PD-1 was upregulated on HIV-specific CD8(+) T cells; PD-1 expression levels were significantly correlated both with viral load and with the reduced capacity for cytokine production and proliferation of HIV-specific CD8(+) T cells. Notably, cytomegalovirus (CMV)-specific CD8(+) T cells from the same donors did not upregulate PD-1 and maintained the production of high levels of cytokines. Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8(+) T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen. The accumulation of HIV-specific dysfunctional CD8(+) T cells in the infected host could prevent the renewal of a functionally competent HIV-specific CD8(+) repertoire.

Amino Acid Sequence↗
PubMed2003

Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice.

We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.

Animals↗
PubMed2024

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3-11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

Humans↗
PubMed2007

Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus.

A regulatory single nucleotide polymorphism (SNP) PD1.3G/A located on programmed cell death 1 (PDCD1) gene, was shown to be involved in susceptibility to systemic lupus erythematosus (SLE) in Swedish, European American, and Mexican cases. However, association to childhood-onset SLE has not been analyzed. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with susceptibility to childhood-onset SLE in Mexican population. Three PDCD1 SNPs, PD1.3G/A, PD1.5C/T, PD1.6G/A, were analyzed in 250 childhood-onset SLE Mexican patients and 355 healthy controls in a case-control association study. Polymorphisms were genotyped by TaqMan technology. Stratification analysis was performed on the SLE cohort to investigate the SNP association with renal disorder. In addition, haplotypes were constructed with these three SNPs. The PD1.3A allele was significantly associated to childhood-onset SLE (P=0.0019, odds ratio (OR) 2.73, 95% confidence interval (95% CI) 1.35-5.56). The other PDCD1 SNPs did not show association. A total of 155 patients (62%) had nephritis, and no association was observed with PDCD1 SNPs. The ACG haplotype (PD1.3A, PD1.5C, PD1.6G) included almost all PD1.3A alleles, and it was more frequent in SLE patients (5.5%) than in controls (2.1%) (P=0.003; OR 2.73, 95% CI 1.37-5.46). The haplotype structure in Mexican controls was significantly different from those reported in Spanish and Swedish. Our results support association of the PD1.3A SNP to susceptibility of childhood-onset SLE in Mexican population and does not show association to lupus nephritis in this age group.

Age of Onset↗