Individual Specificity of the Tumour Antigen

Author(s):  
Pavel Koldovský
1990 ◽  
Vol 9 (9) ◽  
pp. 2937-2943 ◽  
Author(s):  
G. Schiedner ◽  
R. Wessel ◽  
M. Scheffner ◽  
H. Stahl

Nature ◽  
1989 ◽  
Vol 341 (6242) ◽  
pp. 503-507 ◽  
Author(s):  
Duncan McVey ◽  
Leonardo Brizuela ◽  
Ian Mohr ◽  
Daniel R. Marshak ◽  
Yasha Gluzman ◽  
...  

2021 ◽  
Vol 13 ◽  
pp. 175883592098705
Author(s):  
Gao-Na Shi ◽  
Min Hu ◽  
Chengjuan Chen ◽  
Junmin Fu ◽  
Shuai Shao ◽  
...  

Background: Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in adaptive cell-mediated immunity by priming and activating T cells against specific tumour and pathogenic antigens. Methotrexate (MTX), a folate derivative, functions as an immunoregulatory agent. However, the possible effect of MTX on tumour antigen-loaded DCs has not yet been investigated. Methods: We analysed the effect of MTX on the maturation and function of DCs along with tumour cell lysates (TCLs). Using bone marrow-derived DCs, we investigated the effect of MTX combined TCL-loaded DCs on T cells priming and proliferation. We also tested the anti-tumour immune effect on DCs when treated with MTX and/or TCL in vivo. Results: MTX combined with TCL not only enhanced DC maturation and stimulated cytokine release but also promoted CD8+ T cell activation and proliferation. The latter was associated with increased tumour antigen uptake and cross-presentation to T cells. Mechanistically, DC maturation and antigen presentation were partly modulated by NLRP3 inflammasome activation. Furthermore, immunisation of mice with MTX and TCL-pulsed DCs before a tumour challenge significantly delayed tumour onset and retarded its growth. This protective effect was due to priming of IFN-γ releasing CD8+ T cells and enhanced killing of tumour cells by cytotoxic T lymphocytes isolated from these immunised mice. Conclusion: MTX can function as a potent adjuvant in DC vaccines by increasing antigen presentation and T cell priming. Our findings provide a new strategy for the application of DC-based anti-tumour immunotherapy.


PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0118096 ◽  
Author(s):  
Jantipa Jobsri ◽  
Alex Allen ◽  
Deepa Rajagopal ◽  
Michael Shipton ◽  
Kostya Kanyuka ◽  
...  

2003 ◽  
Vol 369 (2) ◽  
pp. 387-398 ◽  
Author(s):  
Jin ZHOU ◽  
Huong T. PHAM ◽  
Ralf RUEDIGER ◽  
Gernot WALTER

Protein phosphatase 2A (PP2A) is very versatile owing to a large number of regulatory subunits and its ability to interact with numerous other proteins. The regulatory A subunit exists as two closely related isoforms designated Aα and Aβ. Mutations have been found in both isoforms in a variety of human cancers. Although Aα has been intensely studied, little is known about Aβ. We generated Aβ-specific antibodies and determined the cell cycle expression, subcellular distribution, and metabolic stability of Aβ in comparison with Aα. Both forms were expressed at constant levels throughout the cell cycle, but Aα was expressed at a much higher level than Aβ. Both forms were found predominantly in the cytoplasm, and both had a half-life of approx. 10h. However, Aα and Aβ differed substantially in their expression patterns in normal tissues and in tumour cell lines. Whereas Aα was expressed at similarly high levels in all tissues and cell lines, Aβ expression varied greatly. In addition, in vivo studies with epitope-tagged Aα and Aβ subunits demonstrated that Aβ is a markedly weaker binder of regulatory B and catalytic C subunits than Aα. Construction of phylogenetic trees revealed that the conservation of Aα during the evolution of mammals is extraordinarily high in comparison with both Aβ and cytochrome c, suggesting that Aα is involved in more protein—protein interactions than Aβ. We also measured the binding of polyoma virus middle tumour antigen and simian virus 40 (SV40) small tumour antigen to Aα and Aβ. Whereas both isoforms bound polyoma virus middle tumour antigen equally well, only Aα bound SV40 small tumour antigen.


PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e42822 ◽  
Author(s):  
Adalberto Costessi ◽  
Nawel Mahrour ◽  
Vikram Sharma ◽  
Rieka Stunnenberg ◽  
Marieke A. Stoel ◽  
...  

2021 ◽  
Author(s):  
Arabzadehghahyazi Negar

file:///C:/Users/MWF/Downloads/Arabzadehghahyazi, Negar.Pre-retrieval Query Performance Prediction (QPP) methods are oblivious to the performance of the retrieval model as they predict query difficulty prior to observing the set of documents retrieved for the query. Among pre-retrieval query performance predictors, specificity-based metrics investigate how corpus, query and corpus-query level statistics can be used to predict the performance of the query. In this thesis, we explore how neural embeddings can be utilized to define corpus-independent and semantics-aware specificity metrics. Our metrics are based on the intuition that a term that is closely surrounded by other terms in the embedding space is more likely to be specific while a term surrounded by less closely related terms is more likely to be generic. On this basis, we leverage geometric properties between embedded terms to define four groups of metrics: (1) neighborhood-based, (2) graph-based, (3) cluster-based and (4) vector-based metrics. Moreover, we employ learning-to-rank techniques to analyze the importance of individual specificity metrics. To evaluate the proposed metrics, we have curated and publicly share a test collection of term specificity measurements defined based on Wikipedia category hierarchy and DMOZ taxonomy. We report on our extensive experiments on the effectiveness of our metrics through metric comparison, ablation study and comparison against the state-of-the-art baselines. We have shown that our proposed set of pre-retrieval QPP metrics based on the properties of pre-trained neural embeddings are more effective for performance prediction compared to the state-of-the-art methods. We report our findings based on Robust04, ClueWeb09 and Gov2 corpora and their associated TREC topics.


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