FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2984963674> ?p ?o ?g. }

• W2984963674 abstract "<h3>Background</h3> Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment. <h3>Methods</h3> Four microsatellite stable PDOs from chemotherapy refractory and one from a treatment naïve CRC were expanded to replicates with 100 million cells each, and HLA class I and class II peptide ligands were analyzed by MS. <h3>Results</h3> We identified an average of 9936 unique peptides per PDO which compares favorably against published immunopeptidomics studies, suggesting high sensitivity. Loss of heterozygosity of the HLA locus was associated with low peptide diversity in one PDO. Peptides from genes without detectable expression by RNA-sequencing were rarely identified by MS. Only 3 out of 612 non-silent mutations encoded for neoantigens that were detected by MS. In contrast, computational HLA binding prediction estimated that 304 mutations could generate neoantigens. One hundred ninety-six of these were located in expressed genes, still exceeding the number of MS-detected neoantigens 65-fold. Treatment of four PDOs with IFNγ upregulated HLA class I expression and qualitatively changed the immunopeptidome, with increased presentation of IFNγ-inducible genes. HLA class II presented peptides increased dramatically with IFNγ treatment. MEK-inhibitor treatment showed no consistent effect on HLA class I or II expression or the peptidome. Importantly, no additional HLA class I or II presented neoantigens became detectable with any treatment. <h3>Conclusions</h3> Only 3 out of 612 non-silent mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this." @default.
• W2984963674 created "2019-11-22" @default.
• W2984963674 creator A5004047300 @default.
• W2984963674 creator A5017097104 @default.
• W2984963674 creator A5017724230 @default.
• W2984963674 creator A5025120810 @default.
• W2984963674 creator A5025409713 @default.
• W2984963674 creator A5026241131 @default.
• W2984963674 creator A5031142553 @default.
• W2984963674 creator A5039870429 @default.
• W2984963674 creator A5044092532 @default.
• W2984963674 creator A5047411547 @default.
• W2984963674 creator A5052539967 @default.
• W2984963674 creator A5056345420 @default.
• W2984963674 creator A5066247182 @default.
• W2984963674 creator A5068159580 @default.
• W2984963674 creator A5072448895 @default.
• W2984963674 creator A5074158782 @default.
• W2984963674 creator A5077300810 @default.
• W2984963674 creator A5079623867 @default.
• W2984963674 creator A5080013197 @default.
• W2984963674 creator A5087479651 @default.
• W2984963674 date "2019-11-18" @default.
• W2984963674 modified "2023-10-10" @default.
• W2984963674 title "Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment" @default.
• W2984963674 cites W1471166809 @default.
• W2984963674 cites W1741548448 @default.
• W2984963674 cites W1842119890 @default.
• W2984963674 cites W1940241680 @default.
• W2984963674 cites W1956285448 @default.
• W2984963674 cites W1991594550 @default.
• W2984963674 cites W2002513358 @default.
• W2984963674 cites W2005704934 @default.
• W2984963674 cites W2042687451 @default.
• W2984963674 cites W2045643041 @default.
• W2984963674 cites W2058884753 @default.
• W2984963674 cites W2066057073 @default.
• W2984963674 cites W2094481139 @default.
• W2984963674 cites W2121626779 @default.
• W2984963674 cites W2159363445 @default.
• W2984963674 cites W2164244787 @default.
• W2984963674 cites W2201214180 @default.
• W2984963674 cites W2214699570 @default.
• W2984963674 cites W2262414037 @default.
• W2984963674 cites W2289851792 @default.
• W2984963674 cites W2345351072 @default.
• W2984963674 cites W2412171122 @default.
• W2984963674 cites W2463195069 @default.
• W2984963674 cites W2518214177 @default.
• W2984963674 cites W2522313999 @default.
• W2984963674 cites W2555228033 @default.
• W2984963674 cites W2586373162 @default.
• W2984963674 cites W2589139221 @default.
• W2984963674 cites W2724264513 @default.
• W2984963674 cites W2728365508 @default.
• W2984963674 cites W2762117293 @default.
• W2984963674 cites W2766220272 @default.
• W2984963674 cites W2766820663 @default.
• W2984963674 cites W2774712455 @default.
• W2984963674 cites W2791512052 @default.
• W2984963674 cites W2792236348 @default.
• W2984963674 cites W2793126529 @default.
• W2984963674 cites W2803570638 @default.
• W2984963674 cites W2885871434 @default.
• W2984963674 cites W2899760200 @default.
• W2984963674 cites W2938645074 @default.
• W2984963674 cites W2945606195 @default.
• W2984963674 cites W2946884236 @default.
• W2984963674 cites W2949273159 @default.
• W2984963674 cites W2960942904 @default.
• W2984963674 cites W2979293383 @default.
• W2984963674 doi "https://doi.org/10.1186/s40425-019-0769-8" @default.
• W2984963674 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6859637" @default.
• W2984963674 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31735170" @default.
• W2984963674 hasPublicationYear "2019" @default.
• W2984963674 type Work @default.
• W2984963674 sameAs 2984963674 @default.
• W2984963674 citedByCount "90" @default.
• W2984963674 countsByYear W29849636742020 @default.
• W2984963674 countsByYear W29849636742021 @default.
• W2984963674 countsByYear W29849636742022 @default.
• W2984963674 countsByYear W29849636742023 @default.
• W2984963674 crossrefType "journal-article" @default.
• W2984963674 hasAuthorship W2984963674A5004047300 @default.
• W2984963674 hasAuthorship W2984963674A5017097104 @default.
• W2984963674 hasAuthorship W2984963674A5017724230 @default.
• W2984963674 hasAuthorship W2984963674A5025120810 @default.
• W2984963674 hasAuthorship W2984963674A5025409713 @default.
• W2984963674 hasAuthorship W2984963674A5026241131 @default.
• W2984963674 hasAuthorship W2984963674A5031142553 @default.
• W2984963674 hasAuthorship W2984963674A5039870429 @default.
• W2984963674 hasAuthorship W2984963674A5044092532 @default.
• W2984963674 hasAuthorship W2984963674A5047411547 @default.
• W2984963674 hasAuthorship W2984963674A5052539967 @default.
• W2984963674 hasAuthorship W2984963674A5056345420 @default.
• W2984963674 hasAuthorship W2984963674A5066247182 @default.
• W2984963674 hasAuthorship W2984963674A5068159580 @default.
• W2984963674 hasAuthorship W2984963674A5072448895 @default.
• W2984963674 hasAuthorship W2984963674A5074158782 @default.
• W2984963674 hasAuthorship W2984963674A5077300810 @default.

• next