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Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.

التفاصيل البيبلوغرافية
العنوان: Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.
المؤلفون: Li YQ; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Luo CL; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Jiang JX; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., He S; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Liu Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Yan WX; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Xia Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Cui Q; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China., Huang Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Lim JQ; Lymphoma Translational Research Laboratory, Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.; ONCO-ACP, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore., Huang D; Lymphoma Translational Research Laboratory, Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.; ONCO-ACP, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore., Hussein IN; Lymphoma Translational Research Laboratory, Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore., Gao Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Lin GW; Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China., Ling YH; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Ma D; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Zhang YT; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Chan JY; Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore., Wei PP; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Wang XX; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Cheng CL; Department of Pathology, Singapore General Hospital, 20 College Road, Academia, 169856, Singapore., Xiong J; State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China., Zhao WL; State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China., Ong CK; Lymphoma Translational Research Laboratory, Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.; Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore., Lim ST; Director's Office, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.; Office of Education, Duke-NUS Medical School, Singapore, 169857, Singapore., Huang HQ; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Peng RJ; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Bei JX; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.; Lymphoma Translational Research Laboratory, Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.
المصدر: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Dec; Vol. 10 (36), pp. e2303913. Date of Electronic Publication: 2023 Nov 10.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Weinheim : WILEY-VCH, [2014]-
مواضيع طبية MeSH: Epstein-Barr Virus Infections*/complications , Epstein-Barr Virus Infections*/pathology , Lymphoma, Extranodal NK-T-Cell*/genetics , Lymphoma, Extranodal NK-T-Cell*/pathology, Humans ; Herpesvirus 4, Human/genetics ; Prognosis ; Single-Cell Analysis ; Tumor Microenvironment
مستخلص: Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1 + malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
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معلومات مُعتمدة: 82130078 National Natural Science Foundation of China; 82261160657 National Natural Science Foundation of China; 201707020039 Sci-Tech Project Foundation of Guangzhou City; 2016ZT06S638 Guangdong Innovative and Entrepreneurial Research Team Program; Chang Jiang Scholars Program; NMRC-OFLCG-18May0028 Singapore Ministry of Health's National Medical Research Council; Tanoto Foundation; Ling Foundation; New Century International Pte Ltd
فهرسة مساهمة: Keywords: DPP4; LMP1+ malignant NK cells; NKTCL; immunosuppression; scRNA-seq
تواريخ الأحداث: Date Created: 20231110 Date Completed: 20231229 Latest Revision: 20240823
رمز التحديث: 20240826
مُعرف محوري في PubMed: PMC10754138
DOI: 10.1002/advs.202303913
PMID: 37949673
قاعدة البيانات: MEDLINE
الوصف
تدمد:2198-3844
DOI:10.1002/advs.202303913