Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report
Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303310/full |
| _version_ | 1827320434719195136 |
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| author | Kewei Zhao Qiuhui Li Pengye Li Tao Liu Xinxiu Liu Fang Zhu Liling Zhang |
| author_facet | Kewei Zhao Qiuhui Li Pengye Li Tao Liu Xinxiu Liu Fang Zhu Liling Zhang |
| author_sort | Kewei Zhao |
| collection | DOAJ |
| description | Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules’ expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases. |
| first_indexed | 2024-04-25T00:46:17Z |
| format | Article |
| id | doaj.art-533d62a832f34482a07cdfc307535e55 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T00:46:17Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-533d62a832f34482a07cdfc307535e552024-03-12T04:26:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13033101303310Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case reportKewei ZhaoQiuhui LiPengye LiTao LiuXinxiu LiuFang ZhuLiling ZhangRelapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules’ expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303310/fulldiffuse large B-cell lymphomasingle-cell RNA sequencingtreatment resistancetumor heterogeneitytumor immune microenvironment |
| spellingShingle | Kewei Zhao Qiuhui Li Pengye Li Tao Liu Xinxiu Liu Fang Zhu Liling Zhang Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report Frontiers in Immunology diffuse large B-cell lymphoma single-cell RNA sequencing treatment resistance tumor heterogeneity tumor immune microenvironment |
| title | Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report |
| title_full | Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report |
| title_fullStr | Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report |
| title_full_unstemmed | Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report |
| title_short | Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report |
| title_sort | single cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory dlbcl a case report |
| topic | diffuse large B-cell lymphoma single-cell RNA sequencing treatment resistance tumor heterogeneity tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303310/full |
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