Experimental Hematology & Oncology最新文献

{"title":"HIV associated lymphoma: latest updates from 2023 ASH annual meeting.","authors":"Chaoyu Wang, Qing Xiao, Xiaomei Zhang, Yao Liu","doi":"10.1186/s40164-024-00530-6","DOIUrl":"10.1186/s40164-024-00530-6","url":null,"abstract":"<p><p>The incidence, clinical characteristics, and prognostic factors of HIV-associated lymphoma remain poorly defined compared to HIV-negative lymphoma. Currently, there are no standard guidelines for treatment of these patients. We summarized several latest reports of HIV associated lymphoma from the 2023 ASH Annual Meeting (ASH2023).</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"65"},"PeriodicalIF":9.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the role of mesenchymal stromal cells in cancer initiation, metastasis and immunosuppression.","authors":"Yanyan Zhang, Charles Wang, Jian Jian Li","doi":"10.1186/s40164-024-00532-4","DOIUrl":"10.1186/s40164-024-00532-4","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) necessitates a thorough understanding of intricate cellular interactions within the tumor microenvironment (TME). Mesenchymal stromal cells (MSCs) play a pivotal role in cancer generation, progression, and immunosuppressive tumor microenvironment. Within the TME, MSCs encompass both resident and circulating counterparts that dynamically communicate and actively participate in TME immunosurveillance and response to ICB. This review aims to reevaluate various facets of MSCs, including their potential self-transformation to function as cancer-initiating cells and contributions to the creation of a conducive environment for tumor proliferation and metastasis. Additionally, we explore the immune regulatory functions of tumor-associated MSCs (TA-MSCs) and MSC-derived extracellular vesicles (MSC-EVs) with analysis of potential connections between circulating and tissue-resident MSCs. A comprehensive understanding of the dynamics of MSC-immune cell communication and the heterogeneous cargo of tumor-educated versus naïve MSCs may unveil a new MSC-mediated immunosuppressive pathway that can be targeted to enhance cancer control by ICB.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"64"},"PeriodicalIF":9.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.","authors":"Jingyuan Li, Jun Tan, Tao Wang, Shan Yu, Guangliang Guo, Kan Li, Le Yang, Bin Zeng, Xueying Mei, Siyong Gao, Xiaomei Lao, Sien Zhang, Guiqing Liao, Yujie Liang","doi":"10.1186/s40164-024-00531-5","DOIUrl":"10.1186/s40164-024-00531-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cancer cells frequently evolve necroptotic resistance to overcome various survival stress during tumorigenesis. However, we have previously showed that necroptosis is widespread in head and neck squamous cell carcinoma (HNSCC) and contributes to tumor progression and poor survival via DAMPs-induced migration and invasiveness in peri-necroptotic tumor cells. This implicated an alternative strategy that cancers cope with necroptotic stress by reprogramming a pro-invasive necroptotic microenvironment (NME). Here, we aim to decipher how necroptotic cells shape the NME and affect HNSCC progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Both our pre-established cellular necroptotic model and newly established Dox-induce intratumoral necroptosis model were used to investigate how necroptosis affect HNSCC progression. Transcriptomic alterations in peri-necroptotic tumor cells were analyzed by RNA-seq and validated in the NME in mice and patients' samples. The differential DAMPs compositon among apopotosis. Necrosis, and necroptosis were analyzed by label-free proteomic technique, and the necroptosis-specific DAMPs were then identified and validated. The potential receptor for ISG15 were simulated using molecular docking and further validated by in vitro assays. Then the ISG15-RAGE axis was blocked by either knockdown of necroptotic-ISG15 release and RAGE inhibitor FPS-ZM1, and the impact on tumor progression were tested. Last, we further tested our findings in a HNSCC-patients cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Necroptosis played a crucial role in driving tumor-cell invasiveness and lymphatic metastasis via tumor-type dependent DAMPs-releasing. Mechanistically, necroptotic DAMPs induced peri-necroptotic EMT via NF-κB and STAT3 signaling. Furthermore, intrinsic orchestration between necroptotic and cGAS-STING signaling resulted in producing a group of interferon stimulated genes (ISGs) as HNSCC-dependent necroptotic DAMPs. Among them, ISG15 played an essential role in reprogramming the NME. We then identified RAGE as a novel receptor for extracellular ISG15. Either blockage of ISG15 release or ISG15-RAGE interaction dramatically impeded necroptosis-driven EMT and lymphatic metastasis in HNSCC. Lastly, clinicopathological analysis showed high ISG15 expression in NME. Extensive necroptosis and high tumor-cell RAGE expression correlated with tumor progression and poor survival of HNSCC patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our data revealed a previously unknown cGAS-ISG15-RAGE dependent reprogramming of the necroptotic microenvironment which converts the necroptotic stress into invasive force to foster HNSCC-cell dissemination. By demonstrating the programmatic production of ISG15 via necroptosis-cGAS orchestration and its downstream signaling through RAGE, we shed light on the unique role of ISG15 in HNSCC progression. Targeting such machineries may hold therapeutic potential for restoring intratumoral survival stress ","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"63"},"PeriodicalIF":9.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunlametinib (HL-085) plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors: an open-label, single-arm, multicenter, phase I study.","authors":"Yuankai Shi, Xiaohong Han, Qian Zhao, YuLong Zheng, Jianhua Chen, Xinmin Yu, Jian Fang, Yutao Liu, Dingzhi Huang, Tianshu Liu, Hong Shen, Suxia Luo, Hongsheng Yu, Yu Cao, Xi Zhang, Pei Hu","doi":"10.1186/s40164-024-00528-0","DOIUrl":"10.1186/s40164-024-00528-0","url":null,"abstract":"<p><strong>Background: </strong>Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors.</p><p><strong>Methods: </strong>Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy.</p><p><strong>Results: </strong>From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1-77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6-14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3-83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3-4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with T_max of 0.5-1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination.</p><p><strong>Conclusions: </strong>Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03781219.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"60"},"PeriodicalIF":10.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-model analysis of gallbladder cancer reveals the role of OxLDL-absorbing neutrophils in promoting liver invasion.","authors":"Dongning Rao, Jiaxin Li, Mao Zhang, Siyuan Huang, Lu Meng, Guohe Song, Jiaqiang Ma, Yingcheng Wu, Yifei Cheng, Shuyi Ji, Gaohua Wu, Lv Chen, Yuming Liu, Yang Shi, Jian Zhou, Fan Jia, Xiaoming Zhang, Ruibin Xi, Qiang Gao","doi":"10.1186/s40164-024-00521-7","DOIUrl":"10.1186/s40164-024-00521-7","url":null,"abstract":"<p><strong>Background: </strong>Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI).</p><p><strong>Results: </strong>Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17⁺ GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils.</p><p><strong>Conclusions: </strong>Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17⁺ GBC cells in GBC-LI.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"58"},"PeriodicalIF":10.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional chromatin landscapes in MLLr AML.","authors":"Pinpin Sui, Zhihong Wang, Peng Zhang, Feng Pan","doi":"10.1186/s40164-024-00523-5","DOIUrl":"10.1186/s40164-024-00523-5","url":null,"abstract":"<p><p>Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"56"},"PeriodicalIF":10.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.","authors":"Zheng Shi, Cuilan Hu, Xiaogang Zheng, Chao Sun, Qiang Li","doi":"10.1186/s40164-024-00519-1","DOIUrl":"10.1186/s40164-024-00519-1","url":null,"abstract":"<p><p>Radiotherapy is one of the mainstream approaches for cancer treatment, although the clinical outcomes are limited due to the radioresistance of tumor cells. Hypoxia and metabolic reprogramming are the hallmarks of tumor initiation and progression and are closely linked to radioresistance. Inside a tumor, the rate of angiogenesis lags behind cell proliferation, and the underdevelopment and abnormal functions of blood vessels in some loci result in oxygen deficiency in cancer cells, i.e., hypoxia. This prevents radiation from effectively eliminating the hypoxic cancer cells. Cancer cells switch to glycolysis as the main source of energy, a phenomenon known as the Warburg effect, to sustain their rapid proliferation rates. Therefore, pathways involved in metabolic reprogramming and hypoxia-induced radioresistance are promising intervention targets for cancer treatment. In this review, we discussed the mechanisms and pathways underlying radioresistance due to hypoxia and metabolic reprogramming in detail, including DNA repair, role of cancer stem cells, oxidative stress relief, autophagy regulation, angiogenesis and immune escape. In addition, we proposed the existence of a feedback loop between energy metabolic reprogramming and hypoxia, which is associated with the development and exacerbation of radioresistance in tumors. Simultaneous blockade of this feedback loop and other tumor-specific targets can be an effective approach to overcome radioresistance of cancer cells. This comprehensive overview provides new insights into the mechanisms underlying tumor radiosensitivity and progression.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"55"},"PeriodicalIF":10.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.","authors":"Shiyong Xin, Xiang Liu, Ziyao Li, Xianchao Sun, Rong Wang, Zhenhua Zhang, Xinwei Feng, Liang Jin, Weiyi Li, Chaozhi Tang, Wangli Mei, Qiong Cao, Haojie Wang, Jianguo Zhang, Lijin Feng, Lin Ye","doi":"10.1186/s40164-024-00517-3","DOIUrl":"10.1186/s40164-024-00517-3","url":null,"abstract":"","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"54"},"PeriodicalIF":10.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of percutaneous thermal ablation and adoptive Th9 cell transfer therapy against non-small cell lung cancer.","authors":"Hanbo Pan, Yu Tian, Siyu Pei, Wanlin Yang, Yanyang Zhang, Zenan Gu, Hongda Zhu, Ningyuan Zou, Jiaqi Zhang, Long Jiang, Yingjie Hu, Shengping Shen, Kai Wang, Haizhen Jin, Ziming Li, Yanyun Zhang, Yichuan Xiao, Qingquan Luo, Hui Wang, Jia Huang","doi":"10.1186/s40164-024-00520-8","DOIUrl":"10.1186/s40164-024-00520-8","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is one of the predominant malignancies globally. Percutaneous thermal ablation (PTA) has gained widespread use among NSCLC patients, with the potential to elicit immune responses but limited therapeutic efficacies for advanced-stage disease. T-helper type 9 (Th9) cells are a subset of CD4⁺ effector T cells with robust and persistent anti-tumor effects. This study proposes to develop PTA-Th9 cell integrated therapy as a potential strategy for NSCLC treatment.</p><p><strong>Methods: </strong>The therapeutic efficacies were measured in mice models with subcutaneously transplanted, recurrence, or lung metastatic tumors. The tumor microenvironments (TMEs) were evaluated by flow cytometry. The cytokine levels were assessed by ELISA. The signaling molecules were determined by quantitative PCR and Western blotting. The translational potential was tested in the humanized NSCLC patient-derived xenograft (PDX) model.</p><p><strong>Results: </strong>We find that PTA combined with adoptive Th9 cell transfer therapy substantially suppresses tumor growth, recurrence, and lung metastasis, ultimately extending the survival of mice with NSCLC grafts, outperforming both PTA and Th9 cell transfer monotherapy. Analysis of TMEs indicates that combinatorial therapy significantly augments tumor-infiltrating Th9 cells, boosts anti-tumor effects of CD8⁺ T cells, and remodels tumor immunosuppressive microenvironments. Moreover, combinatorial therapy significantly strengthens the regional and circulation immune response of CD8⁺ T cells in mice with tumor lung metastasis and induces peripheral CD8⁺ T effector memory cells in mice with tumor recurrence. Mechanically, PTA reinforces the anti-tumor ability of Th9 cells primarily through upregulating interleukin (IL)-1β and subsequently activating the downstream STAT1/IRF1 pathway, which could be effectively blocked by intercepting IL-1β signaling. Finally, the enhanced therapeutic effect of combinatorial therapy is validated in humanized NSCLC PDX models.</p><p><strong>Conclusions: </strong>Collectively, this study demonstrates that combinatorial therapy displays robust and durable anti-tumor efficacy and excellent translational potential, offering excellent prospects for translation and emerging as a promising approach for NSCLC treatment.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"52"},"PeriodicalIF":10.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition.","authors":"Hussein Akil, Hafidha Bentayeb, Marine Aitamer, Chantal Vignoles, Julie Abraham, Nathalie Gachard, Agnès Olivrie, Anne Guyot, Jessica Gobbo, Jean Feuillard, Hamasseh Shirvani, Danielle Troutaud","doi":"10.1186/s40164-024-00518-2","DOIUrl":"10.1186/s40164-024-00518-2","url":null,"abstract":"<p><p>Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1⁺ sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4⁺ and CD8⁺ T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4⁺ and CD8⁺ T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell-cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"53"},"PeriodicalIF":10.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}