FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2557867551> ?p ?o ?g. }

• W2557867551 abstract "Abstract Understanding the elusive mechanisms of tumor-driven immune evasion will aid the refinement of existing cancer immunotherapy strategies and identify novel treatments. To date, pre-clinical animal models that closely model human cancer, including the immune suppressive mechanisms utilized by cancer cells, have been under-characterized. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in non-malignant cells by cancer, we examined T cell function in Eμ-TCL1 transgenic mice as they developed leukemia from 12-months of age. Transgenic expression of TCL1 in B cells had no demonstrable effect on T cells, however, mice with leukemia had decreased in vivo antigen specific T cell activation, suppressed T cell mitogenic proliferation and impaired induction of idiotype specific CD8 T cells capable of killing CLL cells compared to control WT mice (age-matched throughout study) or Eμ-TCL1 transgenic mice without CLL. Leukemic mice also had dysfunctional T cell lymphokine production (Th2-preponderant). To understand the molecular basis for the observed functional defects and to compare changes seen in mice and patients with CLL we performed gene expression profiling. Analysis of highly purified CD4 and CD8 T cells in CLL mice demonstrated altered gene expression profiles compared to WT mice or to young Eμ-TCL1 mice without disease. Of note, infusion of CLL cells into young Eμ-TCL1 mice induced gene expression changes comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T cell defects. Analysis of gene expression changes in T cells in CLL mice compared with those in patients was performed using RESOURCERER, a database for annotating and linking microarray resources within and across species and identified 50 overlapping genes in CD4 T cells and 45 overlapping genes in CD8 T cells. The majority of differentially expressed genes in CD4 T cells from both mice and patients with CLL were involved in cell proliferation and activation pathways with increase in Lck. Multiple defects within the actin cytoskeletal formation pathways were identified in both CD4 and CD8 T cells including Cdc42. Integrity of the T cell cytoskeleton is essential to regulate the dynamic signaling required for T cell activation and effector function in response to immunological recognition of antigen-presenting cells (APCs). T cell conjugates from mice with leukemia had suppressed antigen-dependent F-actin accumulation and early T cell signaling at the immune synapse with CLL cells (APCs) compared to WT mice conjugates. Moreover, we have demonstrated that infusion of CLL cells into young mice induces this T cell defect, demonstrating an in vivo immunomodulating mechanism utilized by tumor cells. Treatment of both CLL cells and autologous T cells from leukemic mice with lenalidomide (0.5 μM for 24 h) enhanced the formation of the F-actin immune synapse and recruitment of tyrosine-phosphorylated proteins irrespective of the presence of exogenous antigen. Of note, the capacity to repair immunological recognition with this agent was associated with increased recruitment of the cytoskeletal signaling molecules Lck and Cdc42 to the immunological synapse, regardless of whether the gene was increased or decreased on gene expression profiling. These results demonstrate that leukemia cells induce changes in multiple T cell pathways regulating antigen recognition and effector function. The similarities with human CLL including reversible immunological synapse dysfunction with an immunomodulating drug validates the use of Eμ-TCL1 mice as a model for further analyses of ways to prevent and reverse cancer-induced immune dysfunction. The use of this model to understand and reverse the molecular changes in T cells induced by leukemia will likely have broad applications to maximize immune responses in patients." @default.
• W2557867551 created "2016-12-08" @default.
• W2557867551 creator A5031749009 @default.
• W2557867551 creator A5037221156 @default.
• W2557867551 creator A5047094317 @default.
• W2557867551 creator A5049134468 @default.
• W2557867551 creator A5067154165 @default.
• W2557867551 creator A5079700663 @default.
• W2557867551 creator A5084245470 @default.
• W2557867551 creator A5087243215 @default.
• W2557867551 date "2008-11-16" @default.
• W2557867551 modified "2023-10-01" @default.
• W2557867551 title "A Mouse Model for Immunotherapeutic Reversal of Leukemia-Induced T Cell Dysfunction" @default.
• W2557867551 doi "https://doi.org/10.1182/blood.v112.11.30.30" @default.
• W2557867551 hasPublicationYear "2008" @default.
• W2557867551 type Work @default.
• W2557867551 sameAs 2557867551 @default.
• W2557867551 citedByCount "0" @default.
• W2557867551 crossrefType "journal-article" @default.
• W2557867551 hasAuthorship W2557867551A5031749009 @default.
• W2557867551 hasAuthorship W2557867551A5037221156 @default.
• W2557867551 hasAuthorship W2557867551A5047094317 @default.
• W2557867551 hasAuthorship W2557867551A5049134468 @default.
• W2557867551 hasAuthorship W2557867551A5067154165 @default.
• W2557867551 hasAuthorship W2557867551A5079700663 @default.
• W2557867551 hasAuthorship W2557867551A5084245470 @default.
• W2557867551 hasAuthorship W2557867551A5087243215 @default.
• W2557867551 hasConcept C121608353 @default.
• W2557867551 hasConcept C154317977 @default.
• W2557867551 hasConcept C167672396 @default.
• W2557867551 hasConcept C202751555 @default.
• W2557867551 hasConcept C203014093 @default.
• W2557867551 hasConcept C2776090121 @default.
• W2557867551 hasConcept C2777701055 @default.
• W2557867551 hasConcept C2778461978 @default.
• W2557867551 hasConcept C2780674031 @default.
• W2557867551 hasConcept C502942594 @default.
• W2557867551 hasConcept C54355233 @default.
• W2557867551 hasConcept C55493867 @default.
• W2557867551 hasConcept C86803240 @default.
• W2557867551 hasConcept C8891405 @default.
• W2557867551 hasConceptScore W2557867551C121608353 @default.
• W2557867551 hasConceptScore W2557867551C154317977 @default.
• W2557867551 hasConceptScore W2557867551C167672396 @default.
• W2557867551 hasConceptScore W2557867551C202751555 @default.
• W2557867551 hasConceptScore W2557867551C203014093 @default.
• W2557867551 hasConceptScore W2557867551C2776090121 @default.
• W2557867551 hasConceptScore W2557867551C2777701055 @default.
• W2557867551 hasConceptScore W2557867551C2778461978 @default.
• W2557867551 hasConceptScore W2557867551C2780674031 @default.
• W2557867551 hasConceptScore W2557867551C502942594 @default.
• W2557867551 hasConceptScore W2557867551C54355233 @default.
• W2557867551 hasConceptScore W2557867551C55493867 @default.
• W2557867551 hasConceptScore W2557867551C86803240 @default.
• W2557867551 hasConceptScore W2557867551C8891405 @default.
• W2557867551 hasLocation W25578675511 @default.
• W2557867551 hasOpenAccess W2557867551 @default.
• W2557867551 hasPrimaryLocation W25578675511 @default.
• W2557867551 hasRelatedWork W1021749332 @default.
• W2557867551 hasRelatedWork W1530333781 @default.
• W2557867551 hasRelatedWork W1746662072 @default.
• W2557867551 hasRelatedWork W1992473608 @default.
• W2557867551 hasRelatedWork W1997867127 @default.
• W2557867551 hasRelatedWork W1998110386 @default.
• W2557867551 hasRelatedWork W1999081675 @default.
• W2557867551 hasRelatedWork W2091038501 @default.
• W2557867551 hasRelatedWork W2141301605 @default.
• W2557867551 hasRelatedWork W2161712070 @default.
• W2557867551 hasRelatedWork W2170056170 @default.
• W2557867551 hasRelatedWork W2489760676 @default.
• W2557867551 hasRelatedWork W2551790524 @default.
• W2557867551 hasRelatedWork W2582360562 @default.
• W2557867551 hasRelatedWork W2586385712 @default.
• W2557867551 hasRelatedWork W2748516568 @default.
• W2557867551 hasRelatedWork W2972334511 @default.
• W2557867551 hasRelatedWork W3015689173 @default.
• W2557867551 hasRelatedWork W3097207450 @default.
• W2557867551 hasRelatedWork W3168736323 @default.
• W2557867551 isParatext "false" @default.
• W2557867551 isRetracted "false" @default.
• W2557867551 magId "2557867551" @default.
• W2557867551 workType "article" @default.