FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3136454705> ?p ?o ?g. }

• W3136454705 endingPage "S183" @default.
• W3136454705 startingPage "S182" @default.
• W3136454705 abstract "Anti-PD-1(L1) therapies appear to be less efficacious in NSCLC patients whose tumors have EGFR activating mutations, but the underlying mechanism is poorly understood. An established computational approach (CIBERSORT) to gene expression profiles of 402 lung adenocarcinoma from TCGA database was applied to infer the proportions of 22 subsets of immune cells in EGFR mutated and wild-type tissue samples. Primary NSCLC resections and peripheral blood of advanced NSCLC patients with determined EGFR status were collected and analyzed the subtypes of immune cells and T cell function via flow cytometry. Pre-treatment and one-cycle of immunotherapy plasma levels of 10 cytokines were measured using Meso Scale Discovery (MSD) in patients treated with immunotherapy. Association between EGFR signaling pathway and IL-10 mRNA expression was analyzed via PCR and western blotting. In vitro re-stimulation model of human CD8+T cells isolated from peripheral blood was used to analyze the impact of different dose of IL-10 on T cells. EGFR-WT tumors were associated with higher proportions of CD8+T (p<0.001) cells and activated memory CD4+ T cells (p<0.001).Transcriptome profiling revealed that lymphocyte activation or functions markers were highly expressed in EGFR-WT tumor. In primary NSCLC resections, EGFR-MUT tumors had lower proportion of CD8+Ki67+T cells (p=0.003). Functional or activated subsets of CD8+T cells, such as CD38+HLA-DR+ and GranzymeB+Ki67+ were also significantly less infiltrated in EGFR-MUT tumors (p=0.016, p=0.013, respectively).CD39, which was recently reported as a novel marker to distinguish bystander TILs (CD39-CD8+) was highly expressed in EGFR-MUT tumors (p=0.012). Similarly, treatment-naïve advanced EGFR-WT patients also had higher percentage of CD8+T cells expressing CD39 in peripheral blood. In addition, CD8+CD39+T cells subset was associated with higher level of Ki67, GranzymeB+Ki67+, PD-1+Ki67+and CD38+HLA-DR+ compared with CD39-T cells. Intratumoral level of IFN-γ, IL-10, IL-1 β, IL-4 was significantly lower in EGFR-MUT tumors compared with WT tumors. To further investigate the role of CD8+T cells expression CD39 and 4 differentially expressing cytokines, we also obtained PBMC from advanced NSCLC patients who received anti-PD1 treatment. Only IL-10 and CD39 were associated with immunotherapy response. In vitro study, 7 tumor cell lines were cocultured with CD8+T cells isolated from healthy donors. CD39+expressing CD8+T cells were significantly increased in the presence of EGFR-WT cell lines than EGFR-MUT cell lines. Also, higher IL-10 was associated with increased proliferation, cytotoxicity of T cells and CD39 expression in dose-dependent manner. To investigate the association of EGFR signaling and IL-10 expression, we added gefitinib in EGFR mutated cell lines and EGF in EGFR-WT cell lines. IL-10 mRNA expression was significantly increased after blocking EGFR signaling pathway and decreased after reactivation of EGFR pathway. Poor response to anti-PD-1 treatment in EGFR patients could be attributed to:1) non-inflammed TME with lower percentage of activated or functional T cell subsets; 2) the abundance of CD39– CD8+ T cells in EGFR-mutated patients. Additional IL-10 could possibly reinvigorate CD8+CD39+T cells to potential anti-PD1 efficacy in EGFR-mutated patients." @default.
• W3136454705 created "2021-03-29" @default.
• W3136454705 creator A5006613618 @default.
• W3136454705 creator A5016049048 @default.
• W3136454705 creator A5054464962 @default.
• W3136454705 creator A5080382748 @default.
• W3136454705 date "2021-03-01" @default.
• W3136454705 modified "2023-10-15" @default.
• W3136454705 title "MA13.06 Deciphering the Characterization of Tumor Microenvironment in EGFR-Mutated Non-Small Cell Lung Cancer" @default.
• W3136454705 doi "https://doi.org/10.1016/j.jtho.2021.01.267" @default.
• W3136454705 hasPublicationYear "2021" @default.
• W3136454705 type Work @default.
• W3136454705 sameAs 3136454705 @default.
• W3136454705 citedByCount "2" @default.
• W3136454705 countsByYear W31364547052022 @default.
• W3136454705 crossrefType "journal-article" @default.
• W3136454705 hasAuthorship W3136454705A5006613618 @default.
• W3136454705 hasAuthorship W3136454705A5016049048 @default.
• W3136454705 hasAuthorship W3136454705A5054464962 @default.
• W3136454705 hasAuthorship W3136454705A5080382748 @default.
• W3136454705 hasBestOaLocation W31364547051 @default.
• W3136454705 hasConcept C121608353 @default.
• W3136454705 hasConcept C126322002 @default.
• W3136454705 hasConcept C143998085 @default.
• W3136454705 hasConcept C167672396 @default.
• W3136454705 hasConcept C203014093 @default.
• W3136454705 hasConcept C2776090121 @default.
• W3136454705 hasConcept C2776107976 @default.
• W3136454705 hasConcept C2776256026 @default.
• W3136454705 hasConcept C2777701055 @default.
• W3136454705 hasConcept C2781182431 @default.
• W3136454705 hasConcept C502942594 @default.
• W3136454705 hasConcept C553184892 @default.
• W3136454705 hasConcept C71924100 @default.
• W3136454705 hasConcept C8891405 @default.
• W3136454705 hasConceptScore W3136454705C121608353 @default.
• W3136454705 hasConceptScore W3136454705C126322002 @default.
• W3136454705 hasConceptScore W3136454705C143998085 @default.
• W3136454705 hasConceptScore W3136454705C167672396 @default.
• W3136454705 hasConceptScore W3136454705C203014093 @default.
• W3136454705 hasConceptScore W3136454705C2776090121 @default.
• W3136454705 hasConceptScore W3136454705C2776107976 @default.
• W3136454705 hasConceptScore W3136454705C2776256026 @default.
• W3136454705 hasConceptScore W3136454705C2777701055 @default.
• W3136454705 hasConceptScore W3136454705C2781182431 @default.
• W3136454705 hasConceptScore W3136454705C502942594 @default.
• W3136454705 hasConceptScore W3136454705C553184892 @default.
• W3136454705 hasConceptScore W3136454705C71924100 @default.
• W3136454705 hasConceptScore W3136454705C8891405 @default.
• W3136454705 hasIssue "3" @default.
• W3136454705 hasLocation W31364547051 @default.
• W3136454705 hasOpenAccess W3136454705 @default.
• W3136454705 hasPrimaryLocation W31364547051 @default.
• W3136454705 hasRelatedWork W2904909612 @default.
• W3136454705 hasRelatedWork W2912621681 @default.
• W3136454705 hasRelatedWork W3025154575 @default.
• W3136454705 hasRelatedWork W3039388108 @default.
• W3136454705 hasRelatedWork W3120170523 @default.
• W3136454705 hasRelatedWork W3214468520 @default.
• W3136454705 hasRelatedWork W4286629873 @default.
• W3136454705 hasRelatedWork W4327715451 @default.
• W3136454705 hasRelatedWork W4362003594 @default.
• W3136454705 hasRelatedWork W4366590730 @default.
• W3136454705 hasVolume "16" @default.
• W3136454705 isParatext "false" @default.
• W3136454705 isRetracted "false" @default.
• W3136454705 magId "3136454705" @default.
• W3136454705 workType "article" @default.