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PD-1 Blockade Reinvigorates Bone Marrow CD8 + T Cells from Patients with Multiple Myeloma in the Presence of TGFβ Inhibitors
DC Field | Value | Language |
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dc.contributor.author | 조현수 | - |
dc.date.accessioned | 2021-09-29T00:29:00Z | - |
dc.date.available | 2021-09-29T00:29:00Z | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/183859 | - |
dc.description.abstract | Purpose: Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma. Experimental design: Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti-PD-1 and TGFβ inhibitors. Results: We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1-expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti-PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti-PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFβ, which was overexpressed by myeloma cells. Conclusions: Our findings indicate that combined blockade of PD-1 and TGFβ may be useful for the treatment of multiple myeloma. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Aged, 80 and over | - |
dc.subject.MESH | Antibodies, Monoclonal / pharmacology* | - |
dc.subject.MESH | Bone Marrow / drug effects | - |
dc.subject.MESH | Bone Marrow / immunology* | - |
dc.subject.MESH | Bone Marrow / pathology | - |
dc.subject.MESH | CD8-Positive T-Lymphocytes / immunology* | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Multiple Myeloma / drug therapy* | - |
dc.subject.MESH | Multiple Myeloma / immunology | - |
dc.subject.MESH | Multiple Myeloma / pathology | - |
dc.subject.MESH | Programmed Cell Death 1 Receptor / antagonists & inhibitors* | - |
dc.subject.MESH | Programmed Cell Death 1 Receptor / immunology | - |
dc.subject.MESH | Receptors, Antigen, T-Cell / immunology* | - |
dc.subject.MESH | Transforming Growth Factor beta / antagonists & inhibitors* | - |
dc.subject.MESH | Transforming Growth Factor beta / metabolism | - |
dc.title | PD-1 Blockade Reinvigorates Bone Marrow CD8 + T Cells from Patients with Multiple Myeloma in the Presence of TGFβ Inhibitors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Minsuk Kwon | - |
dc.contributor.googleauthor | Chang Gon Kim | - |
dc.contributor.googleauthor | Hoyoung Lee | - |
dc.contributor.googleauthor | Hyunsoo Cho | - |
dc.contributor.googleauthor | Youngun Kim | - |
dc.contributor.googleauthor | Eung Chang Lee | - |
dc.contributor.googleauthor | Seong Jin Choi | - |
dc.contributor.googleauthor | Junsik Park | - |
dc.contributor.googleauthor | In-Ho Seo | - |
dc.contributor.googleauthor | Bjarne Bogen | - |
dc.contributor.googleauthor | Ik-Chan Song | - |
dc.contributor.googleauthor | Deog-Yeon Jo | - |
dc.contributor.googleauthor | Jin Seok Kim | - |
dc.contributor.googleauthor | Su-Hyung Park | - |
dc.contributor.googleauthor | Inhak Choi | - |
dc.contributor.googleauthor | Yoon Seok Choi | - |
dc.contributor.googleauthor | Eui-Cheol Shin | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-19-0267 | - |
dc.contributor.localId | A05991 | - |
dc.contributor.localId | A05788 | - |
dc.contributor.localId | A03929 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 31941832 | - |
dc.contributor.affiliatedAuthor | 조현수 | - |
dc.citation.volume | 26 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1644 | - |
dc.citation.endPage | 1655 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.26(7) : 1644-1655, 2020-04 | - |
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