| Autor: |
Eui-Cheol Shin, Yoon Seok Choi, Inhak Choi, Su-Hyung Park, Jin Seok Kim, Deog-Yeon Jo, Ik-Chan Song, Bjarne Bogen, In-Ho Seo, Junsik Park, Seong Jin Choi, Eung Chang Lee, Youngun Kim, Hyunsoo Cho, Hoyoung Lee, Chang Gon Kim, Minsuk Kwon |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6528777 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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