scholarly journals The Role of Soluble Programmed Death Protein 1 in Immunosuppression of Sepsis and its Estimation Value in Prognosis

2021 ◽  
Vol 83 (s5) ◽  
Author(s):  
J. Zhong ◽  
Xiaoyue Li ◽  
W. Zhang ◽  
D. Chen ◽  
L. Y. Zhang ◽  
...  
Keyword(s):  
Programmed Death ◽  
Programmed Death Protein 1

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

scholarly journals The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 114 ◽  
Author(s):  
Ping-Chih Hsu ◽  
Cheng-Ta Yang ◽  
David Jablons ◽  
Liang You
Keyword(s):  
Immune Responses ◽  
Immune Checkpoint ◽  
T Cell Tolerance ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Anti Cancer ◽  
Thoracic Cancer ◽  
Future Work ◽  
Human Nsclc

The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM. YAP has been suggested as a new therapeutic target in NSCLC and MPM. The role of YAP in regulating tumor immunity such as PD-L1 expression has just begun to be explored, and the correlation between YAP-induced tumorigenesis and host anti-tumor immune responses is not well known. Here, we review recent studies investigating the correlation between YAP and PD-L1 and demonstrating the mechanism by which YAP regulates PD-L1 expression in human NSCLC and MPM. Future work should focus on the interactions between Hippo/YAP signaling pathways and the immune checkpoint PD-L1/PD-1 pathway. The development of new synergistic drugs for immune checkpoint PD-L1/PD-1 blockade in NSCLC and MPM is warranted.

scholarly journals Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice: The Paradox in Transgenic Models

Diabetes ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 1861-1869 ◽  
Author(s):  
C.-J. Wang ◽  
F.-C. Chou ◽  
C.-H. Chu ◽  
J.-C. Wu ◽  
S.-H. Lin ◽  
...  
Keyword(s):  
Protective Role ◽  
Diabetic Mice ◽  
Transgenic Models ◽  
Nonobese Diabetic ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nonobese Diabetic Mice

scholarly journals Deubiquitination and Stabilization of PD-L1 by USP21

2021 ◽  
Author(s):  
Shuying Yang ◽  
Youqian Wu ◽  
Huanhuan Yan ◽  
Bing Shan ◽  
Dongheng Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Mass Spectrometry Analysis ◽  
Polyubiquitin Chains ◽  
Spectrometry Analysis ◽  
Protein Levels ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
Novel Strategy

Abstract Background: The immunotherapy for different types of cancers that targeting programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) has highlighted the importance of suppressing specific T cell responses. Recently, several studies have shown that the expression level of PD-L1 in tumor cells is positively correlated with tumor metastasis as well as recurrence rate. The potent effects of post-translational modifications (PTMs) for PD-L1, such as ubiquitination, glycosylation, phosphorylation and palmitoylation, have been reported to be related to immunosuppression. However, the regulation of PD-L1 degradation in cancers is still not well understood. In this paper, we mainly investigate the deubiquitination regulation of PD-L1. Methods: The protein levels of PD-L1 and USP21 were detected by Immunoblotting and immunohistochemistry. The interaction between PD-L1 and USP21 was determined by co-immunoprecipitation. The deubiquitination of PD-L1 was determined by in vitro deubiquitination assay. The deubiquitination sites of PD-L1 were identified by mass spectrometry analysis. The expression of mRNA in target tissues was presented by bioinformatics analysis.Results: Overexpression of USP21 significantly increased PD-L1 abundance and knockdown of USP21 induced degradation of PD-L1. In vitro deubiquitination assay showed that USP21-WT reduced polyubiquitin chains from PD-L1 while USP21-C221A did not. Furthermore, five lysines in intracellular segment of PD-L1 are potential deubiquitin sites and cancer-derived mutations of PD-L1 in Asp276 have the ability to enhance the deubiquitination of PD-L1 mediated by USP21. Finally, we found that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification co-occurs with the upregulation of PD-L1 levels. Moreover, IHC analysis showed stronger staining of PD-L1 and USP21 in lung cancer samples than adjacent tissues. Conclusion: We identified USP21 as a novel deubiquitinase of PD-L1. Hopefully, targeting PD-L1 by inhibiting USP21 might be a potentially novel strategy for the treatment of lung cancer.

scholarly journals Role of PDL1 as a prognostic marker in renal cell carcinoma: a prospective observational study in eastern India

2019 ◽  
Vol 11 ◽  
pp. 175628721986885
Author(s):  
Barun Kumar ◽  
Amlan Ghosh ◽  
Chhanda Datta ◽  
Dilip Kumar Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Disease Recurrence ◽  
Programmed Death ◽  
Specific Mortality ◽  
Cancer Specific Mortality

Background: Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies. Programmed death ligand-1 (PDL1) is an immune checkpoint inhibitor, instrumental in ‘T cell escape’ of malignant cells. PDL1 has been shown to be associated with poor prognosis in multiple small studies. In this study, we want to study the role of PDL1 as a prognostic marker in RCC in an Indian population. Methods: A total of 30 patients who underwent radical or partial nephrectomy, with histopathological findings of RCC, were included in the study. PDL1 expression was studied in tumour tissue with immunohistochemistry. Patients were followed up for a period of 2 years for disease recurrence and cancer-specific mortality. Results: Expression of PDL1 was seen to be associated with higher grade and stage at presentation. PDL1 expression was also associated with statistically significant increased incidence of disease recurrence. Although cancer-specific mortality was higher in patients with positive PDL1 expression, it was seen to be statistically insignificant. Conclusions: PDL1 is a novel prognostic marker for RCC and is associated with poor prognosis. More studies with larger patient pool and multicentric studies will establish the role of PDL1 with certainty. This can be the torchbearer for the future management of RCC.

scholarly journals PD-L1 Expression Patterns in Microsatellite Instability-High Intestinal Adenocarcinoma Subtypes

2019 ◽  
Vol 152 (3) ◽  
pp. 384-391 ◽  
Author(s):  
Jordan Roberts ◽  
Safia N Salaria ◽  
Justin Cates ◽  
Yang Wang ◽  
Cindy Vnencak-Jones ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Tumor Cells ◽  
Mucinous Adenocarcinoma ◽  
Expression Patterns ◽  
Inflammatory Cells ◽  
Medullary Carcinoma ◽  
Molecular Features ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
Histologic Subtypes

Abstract Objectives To investigate patterns of programmed death protein-1 (PD-L1) expression in microsatellite instability (MSI)-high intestinal carcinomas and correlate them with pathologic and molecular features. Methods One hundred and fifteen MSI-high and 41 microsatellite stable carcinomas were included. Tumor sections were immunohistochemically labeled for PD-L1. The results were correlated with histologic subtypes, MSI, and BRAF status. Results As expected, MSI status was associated with PD-L1 expression. Among 115 MSI-high tumors, PD-L1 expression was observed on tumor cells in 28 tumors and on tumor-associated inflammatory cells in 77 tumors. Medullary carcinoma demonstrated more frequent PD-L1 expression on tumor cells than mucinous and typical adenocarcinoma. PD-L1 expression was more frequent in medullary and typical adenocarcinoma than in mucinous adenocarcinoma based on combined positive scores. Tumors with more nucleotide shifts by PCR-based MSI testing were more likely to express PD-L1. Conclusions Expression of PD-L1 is different among different histologic subtypes of MSI-high intestinal carcinomas.

Sign in / Sign up

Export Citation Format

Share Document