PMID- 38533514 OWN - NLM STAT- MEDLINE DCOM- 20240328 LR - 20240402 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 15 DP - 2024 TI - Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report. PG - 1303310 LID - 10.3389/fimmu.2024.1303310 [doi] LID - 1303310 AB - 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. CI - Copyright (c) 2024 Zhao, Li, Li, Liu, Liu, Zhu and Zhang. FAU - Zhao, Kewei AU - Zhao K AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Qiuhui AU - Li Q AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Pengye AU - Li P AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Tao AU - Liu T AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Xinxiu AU - Liu X AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhu, Fang AU - Zhu F AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Liling AU - Zhang L AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Case Reports DEP - 20240312 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 SB - IM MH - Humans MH - Transcriptome MH - Neoplasm Recurrence, Local/drug therapy MH - *Lymphoma, Large B-Cell, Diffuse/pathology MH - *Lymphoma, Non-Hodgkin/drug therapy MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Tumor Microenvironment PMC - PMC10963401 OTO - NOTNLM OT - diffuse large B-cell lymphoma OT - single-cell RNA sequencing OT - treatment resistance OT - tumor heterogeneity OT - tumor immune microenvironment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/03/27 06:44 MHDA- 2024/03/28 06:44 PMCR- 2024/01/01 CRDT- 2024/03/27 03:59 PHST- 2023/09/27 00:00 [received] PHST- 2024/02/21 00:00 [accepted] PHST- 2024/03/28 06:44 [medline] PHST- 2024/03/27 06:44 [pubmed] PHST- 2024/03/27 03:59 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2024.1303310 [doi] PST - epublish SO - Front Immunol. 2024 Mar 12;15:1303310. doi: 10.3389/fimmu.2024.1303310. eCollection 2024.