Topic
PTPRC
About: PTPRC is a research topic. Over the lifetime, 157 publications have been published within this topic receiving 3899 citations. The topic is also known as: CD45 antigen & T200.
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TL;DR: The human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in colon carcinogenesis, and the amount of tissue F nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue.
Abstract: Importance Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests thatFusobacterium nucleatummay promote colonic neoplasia development by downregulating antitumor T cell–mediated adaptive immunity. Objective To test the hypothesis that a greater amount ofF nucleatumin colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue. Design, Setting, and Participants A cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses’ Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount ofF nucleatumin colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount ofF nucleatumwith densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, andKRAS,BRAF, andPIK3CAmutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing. Main Outcomes and Measures Densities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis. Results F nucleatumwas detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared withF nucleatum–negative cases,F nucleatum–high cases were inversely associated with the density of CD3+T cells (for a unit increase in quartile categories of CD3+T cells as an outcome: multivariable odds ratio, 0.47 [95% CI, 0.26-0.87];Pfor trend = .006). The amount ofF nucleatumwas not significantly associated with the density of CD8+, CD45RO+, or FOXP3+T cells (P fortrend = .24, .88, and .014, respectively). Conclusions and Relevance The amount of tissueF nucleatumis inversely associated with CD3+T-cell density in colorectal carcinoma tissue. On validation, our human population data may provide an impetus for further investigations on potential interactive roles ofFusobacteriumand host immunity in colon carcinogenesis.
438 citations
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TL;DR: The PTPRC mutation is found to be linked to and associated with the disease in three MS nuclear families and the same variant CD45 phenotype, with an as-yet-unknown origin, among the members affected with MS is found.
Abstract: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is widely accepted that a dysregulated immune response against brain resident antigens is central to its yet unknown pathogenesis1,2,3,4. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown5,6,7. Here we investigated the role of a point mutation in the gene (PTPRC) encoding protein-tyrosine phosphatase, receptor-type C (also known as CD45) in the heterozygous state in the development of MS. The nucleotide transition in exon 4 of the gene locus interferes with mRNA splicing and results in altered expression of CD45 isoforms on immune cells. In three of four independent case-control studies, we demonstrated an association of the mutation with MS. We found the PTPRC mutation to be linked to and associated with the disease in three MS nuclear families. In one additional family, we found the same variant CD45 phenotype, with an as-yet-unknown origin, among the members affected with MS. Our findings suggest an association of the mutation in PTPRC with the development of MS in some families.
200 citations
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TL;DR: Tumour CD274 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T cells in the tumour microenvironment.
Abstract: Objective Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. Design We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses9 Health Study and Health Professionals Follow-up Study. We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3 + , CD8 + , CD45RO (PTPRC) + or FOXP3 + cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level and KRAS , BRAF and PIK3CA mutations. Results CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. Tumour CD274 expression level correlated inversely with FOXP3 + cell density in colorectal cancer tissue (outcome) (p trend =0.0002). For a unit increase in outcome quartile categories, multivariable OR in the highest (vs lowest) CD274 expression score was 0.22 (95% CI 0.10 to 0.47). Tumour CD274 expression was inversely associated with MSI-high status (p=0.001). CD274 expression was not significantly associated with CD3 + , CD8 + or CD45RO + cell density, pathological lymphocytic reactions or patient survival prognosis. Conclusions Tumour CD274 expression is inversely associated with FOXP3 + cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T cells in the tumour microenvironment.
173 citations
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TL;DR: It is proposed that high wild-type CD45 expression is necessary to dephosphorylate p56(lck) pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity and is explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting p tyr-505 and positively acting pT Tyr-394 tyrosine kinase phosphorylation sites.
170 citations
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TL;DR: The possibility that PTPs regulating the immune system may serve as therapeutic targets is discussed, as well as the leading examples include the allelic variant of the lymphoid tyrosine phosphatase (PTPN22), which is associated with multiple autoimmune diseases.
Abstract: Protein tyrosine phosphatases (PTPs) are important regulators of many cellular functions and a growing number of PTPs have been implicated in human disease conditions, such as developmental defects, neoplastic disorders, and immunodeficiency. Here, we review the involvement of PTPs in human autoimmunity. The leading examples include the allelic variant of the lymphoid tyrosine phosphatase (PTPN22), which is associated with multiple autoimmune diseases, and mutations that affect the exon-intron splicing of CD45 (PTPRC). We also find it likely that additional PTPs are involved in susceptibility to autoimmune and inflammatory diseases. Finally, we discuss the possibility that PTPs regulating the immune system may serve as therapeutic targets.
169 citations