{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Thounaojam MC"],"funding":["NCRR NIH HHS","NIDA NIH HHS","NHLBI NIH HHS","NIMHD NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["32439-55"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4741704"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(32)"],"pubmed_abstract":["The immunosuppressive tumor microenvironment usurps host antitumor immunity by multiple mechanisms including interference with the Notch system, which is important for various metazoan cell fate decisions and hematopoietic cell differentiation and function. We observed that treatment with the proteasome inhibitor bortezomib in mice bearing various solid tumors resulted in an upregulated expression of various Notch signaling components in lymphoid tissues, thereby increasing CD8+T-lymphocyte IFNγ secretion and expression of effector molecules, perforin and granzyme B, as well as the T-box transcription factor eomesodermin. Bortezomib also neutralized TGFβ-mediated suppression of IFNγ and granzyme B expression in activated CD8+T-cells. Of note, bortezomib reversed tumor-induced downregulatio"],"journal":["Oncotarget"],"pubmed_title":["Bortezomib enhances expression of effector molecules in anti-tumor CD8+ T lymphocytes by promoting Notch-nuclear factor-κB crosstalk."],"pmcid":["PMC4741704"],"funding_grant_id":["T32 HL007737","R25 GM059994","CA182843","R24 DA036420","U54CA163069","U54 MD007593","R01 CA175370","U54 CA163069","G12 MD007586","SC1 CA182843","T32 5T32HL007737","S10 RR0254970","P50 CA090949"],"pubmed_authors":["Carbone DP","Dikov MM","Dudimah DF","Shanker A","Thounaojam MC","Pellom ST","Uzhachenko RV"],"additional_accession":[]},"is_claimable":false,"name":"Bortezomib enhances expression of effector molecules in anti-tumor CD8+ T lymphocytes by promoting Notch-nuclear factor-κB crosstalk.","description":"The immunosuppressive tumor microenvironment usurps host antitumor immunity by multiple mechanisms including interference with the Notch system, which is important for various metazoan cell fate decisions and hematopoietic cell differentiation and function. We observed that treatment with the proteasome inhibitor bortezomib in mice bearing various solid tumors resulted in an upregulated expression of various Notch signaling components in lymphoid tissues, thereby increasing CD8+T-lymphocyte IFNγ secretion and expression of effector molecules, perforin and granzyme B, as well as the T-box transcription factor eomesodermin. Bortezomib also neutralized TGFβ-mediated suppression of IFNγ and granzyme B expression in activated CD8+T-cells. Of note, bortezomib reversed tumor-induced downregulatio","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Oct","modification":"2025-05-18T10:34:11.837Z","creation":"2025-05-18T10:34:11.837Z"},"accession":"S-EPMC4741704","cross_references":{"pubmed":["26431276"],"doi":["10.18632/oncotarget.5857"]}}