FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980680922> ?p ?o ?g. }

• W2980680922 endingPage "e29" @default.
• W2980680922 startingPage "e29" @default.
• W2980680922 abstract "The investigation of the differentiation of terminal effector CD8+CD57+T cells (TTE) in multiple myeloma (MM) and its premalignant stage, monoclonal gammopathy of undetermined significance (MGUS), is essential for understanding myeloma immune escape. We have previously shown that patients with clonal expansions of cytotoxic TTE cells have better outcomes than those who do not, but have not examined the underlining differentiation of TTE cells that leads to these distinct states. We hypothesised that a lack of clonally expanded TTE cells in myeloma patients could be due to myeloma induced alterations of TTE cell differentiation. To define TTE cell differentiation at high resolution, we have analysed paired bone marrow (BM) and peripheral blood (PB) samples from patients with newly diagnosed Myeloma (NDMM) and MGUS using time of flight mass cytometry and unsupervised clustering algorithm Flow Self-organizing Map (FlowSOM). We designed a 39 antibody panel, including antibodies to TCR-Vβ families custom-labelled with heavy metals, allowing the detailed characterization of the phenotype of clonally expanded TTE cells. We found that in contrast to TTE cells in MGUS, TTE cells in BM of NDMM failed to display the phenotype typical of terminal effector cell differentiation and were enriched in atypical tissue resident CD69+, CD28+ and CD27+ subsets. They also failed to display the expected upregulation of CD45RA and downregulation of CD45RO expression. Moreover the accumulation of atypical CD69+ TTE cells was prevalent in myeloma patients without clonally expanded TTE cells. FlowSOM clustering discovered 4 metaclusters (MC) contributing to the accumulation of CD69+ TTE cells in the BM of NDMM patients. Phenotypically, two MC were in the memory stage based on CD27, CD28 and CD45RO expression and another two MC showed evidence of progression to the effector stage by downregulating CD27, CD28, CD45RO and upregulating CD45RA expression. Progression to the effector stage was associated with downregulation of CD38 and PD-1 expression, but did not affect persistent TIGIT expression. Vβ expanded TTE cells did not contribute to the accumulation of CD69+ TTE cells and occupied phenotypically different MC with low or undetectable CD69 expression. When comparing phenotype of Vβ expanded TTE cells to remaining TTE cells, effector and memory CD8+T cells they had higher Tbet, Perforin, Granzyme B, and lower levels of Eomes, TIGIT and PD-1 expression arguing against their exhaustion stage and confirming our previous observations that they resemble senescent cells Our results suggest that accumulation of atypical tissue resident CD69+ TTE cells in myeloma infiltrated BM could prevent differentiation and expansion of clonal myeloma specific CD8+TTE cells and ultimately contribute to myeloma immune escape." @default.
• W2980680922 created "2019-10-25" @default.
• W2980680922 creator A5003349200 @default.
• W2980680922 creator A5004715557 @default.
• W2980680922 creator A5005357516 @default.
• W2980680922 creator A5005615806 @default.
• W2980680922 creator A5006212636 @default.
• W2980680922 creator A5009395461 @default.
• W2980680922 creator A5015360282 @default.
• W2980680922 creator A5023896269 @default.
• W2980680922 creator A5026056839 @default.
• W2980680922 creator A5041267811 @default.
• W2980680922 creator A5045908960 @default.
• W2980680922 creator A5046710654 @default.
• W2980680922 creator A5047415265 @default.
• W2980680922 creator A5064909992 @default.
• W2980680922 creator A5077240208 @default.
• W2980680922 creator A5080617550 @default.
• W2980680922 creator A5087490834 @default.
• W2980680922 date "2019-10-01" @default.
• W2980680922 modified "2023-09-25" @default.
• W2980680922 title "Accumulation of CD69+ Terminal Effector CD8+ T cells occurs in the bone marrow of newly diagnosed Myeloma patients who lack protective clonal Vb expanded cytotoxic T cells" @default.
• W2980680922 doi "https://doi.org/10.1016/j.clml.2019.09.043" @default.
• W2980680922 hasPublicationYear "2019" @default.
• W2980680922 type Work @default.
• W2980680922 sameAs 2980680922 @default.
• W2980680922 citedByCount "0" @default.
• W2980680922 crossrefType "journal-article" @default.
• W2980680922 hasAuthorship W2980680922A5003349200 @default.
• W2980680922 hasAuthorship W2980680922A5004715557 @default.
• W2980680922 hasAuthorship W2980680922A5005357516 @default.
• W2980680922 hasAuthorship W2980680922A5005615806 @default.
• W2980680922 hasAuthorship W2980680922A5006212636 @default.
• W2980680922 hasAuthorship W2980680922A5009395461 @default.
• W2980680922 hasAuthorship W2980680922A5015360282 @default.
• W2980680922 hasAuthorship W2980680922A5023896269 @default.
• W2980680922 hasAuthorship W2980680922A5026056839 @default.
• W2980680922 hasAuthorship W2980680922A5041267811 @default.
• W2980680922 hasAuthorship W2980680922A5045908960 @default.
• W2980680922 hasAuthorship W2980680922A5046710654 @default.
• W2980680922 hasAuthorship W2980680922A5047415265 @default.
• W2980680922 hasAuthorship W2980680922A5064909992 @default.
• W2980680922 hasAuthorship W2980680922A5077240208 @default.
• W2980680922 hasAuthorship W2980680922A5080617550 @default.
• W2980680922 hasAuthorship W2980680922A5087490834 @default.
• W2980680922 hasBestOaLocation W29806809222 @default.
• W2980680922 hasConcept C148125776 @default.
• W2980680922 hasConcept C154317977 @default.
• W2980680922 hasConcept C159654299 @default.
• W2980680922 hasConcept C163864487 @default.
• W2980680922 hasConcept C167672396 @default.
• W2980680922 hasConcept C202751555 @default.
• W2980680922 hasConcept C203014093 @default.
• W2980680922 hasConcept C2776364478 @default.
• W2980680922 hasConcept C2777250017 @default.
• W2980680922 hasConcept C2780007613 @default.
• W2980680922 hasConcept C502942594 @default.
• W2980680922 hasConcept C542903549 @default.
• W2980680922 hasConcept C54355233 @default.
• W2980680922 hasConcept C86803240 @default.
• W2980680922 hasConcept C8891405 @default.
• W2980680922 hasConceptScore W2980680922C148125776 @default.
• W2980680922 hasConceptScore W2980680922C154317977 @default.
• W2980680922 hasConceptScore W2980680922C159654299 @default.
• W2980680922 hasConceptScore W2980680922C163864487 @default.
• W2980680922 hasConceptScore W2980680922C167672396 @default.
• W2980680922 hasConceptScore W2980680922C202751555 @default.
• W2980680922 hasConceptScore W2980680922C203014093 @default.
• W2980680922 hasConceptScore W2980680922C2776364478 @default.
• W2980680922 hasConceptScore W2980680922C2777250017 @default.
• W2980680922 hasConceptScore W2980680922C2780007613 @default.
• W2980680922 hasConceptScore W2980680922C502942594 @default.
• W2980680922 hasConceptScore W2980680922C542903549 @default.
• W2980680922 hasConceptScore W2980680922C54355233 @default.
• W2980680922 hasConceptScore W2980680922C86803240 @default.
• W2980680922 hasConceptScore W2980680922C8891405 @default.
• W2980680922 hasIssue "10" @default.
• W2980680922 hasLocation W29806809221 @default.
• W2980680922 hasLocation W29806809222 @default.
• W2980680922 hasOpenAccess W2980680922 @default.
• W2980680922 hasPrimaryLocation W29806809221 @default.
• W2980680922 hasRelatedWork W115137046 @default.
• W2980680922 hasRelatedWork W1971653835 @default.
• W2980680922 hasRelatedWork W1971852928 @default.
• W2980680922 hasRelatedWork W1997787000 @default.
• W2980680922 hasRelatedWork W2023756150 @default.
• W2980680922 hasRelatedWork W2068084502 @default.
• W2980680922 hasRelatedWork W2147423551 @default.
• W2980680922 hasRelatedWork W2333239088 @default.
• W2980680922 hasRelatedWork W2893011256 @default.
• W2980680922 hasRelatedWork W2953107159 @default.
• W2980680922 hasVolume "19" @default.
• W2980680922 isParatext "false" @default.
• W2980680922 isRetracted "false" @default.
• W2980680922 magId "2980680922" @default.
• W2980680922 workType "article" @default.