دورية أكاديمية
Mass cytometry of Hodgkin lymphoma reveals a CD4 + regulatory T-cell-rich and exhausted T-effector microenvironment.
| العنوان: | Mass cytometry of Hodgkin lymphoma reveals a CD4 + regulatory T-cell-rich and exhausted T-effector microenvironment. |
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| المؤلفون: | Cader FZ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Schackmann RCJ; Department of Cell Biology, Harvard Medical School, Boston, MA., Hu X; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.; Harvard T.H. Chan School of Public Health, Boston, MA., Wienand K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Redd R; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.; Harvard T.H. Chan School of Public Health, Boston, MA., Chapuy B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Ouyang J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Paul N; Longwood Medical Area CyTOF Core Facility, Dana-Farber Cancer Institute, Boston, MA., Gjini E; Department of Pathology, Brigham and Women's Hospital, Boston, MA; and., Lipschitz M; Department of Pathology, Brigham and Women's Hospital, Boston, MA; and., Armand P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Wu D; Department of Pathology, University of Washington, Seattle, WA., Fromm JR; Department of Pathology, University of Washington, Seattle, WA., Neuberg D; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.; Harvard T.H. Chan School of Public Health, Boston, MA., Liu XS; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.; Harvard T.H. Chan School of Public Health, Boston, MA., Rodig SJ; Department of Pathology, Brigham and Women's Hospital, Boston, MA; and., Shipp MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. |
| المصدر: | Blood [Blood] 2018 Aug 23; Vol. 132 (8), pp. 825-836. Date of Electronic Publication: 2018 Jun 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Cytophotometry*, Biomarkers, Tumor/*immunology , Hodgkin Disease/*immunology , Reed-Sternberg Cells/*immunology , T-Lymphocytes, Regulatory/*immunology , Tumor Microenvironment/*immunology, Hodgkin Disease/pathology ; Humans ; Reed-Sternberg Cells/pathology ; T-Lymphocytes, Regulatory/pathology |
| مستخلص: | In classical Hodgkin lymphoma (cHL), the host antitumor immune response is ineffective. Hodgkin Reed-Sternberg (HRS) cells have multifaceted mechanisms to evade the immune system, including 9p24.1 /CD274(PD-L1)/PDCD1LG2(PD-L2) genetic alterations, overexpression of PD-1 ligands, and associated T-cell exhaustion and additional structural bases of aberrant antigen presentation. The clinical success of PD-1 blockade in cHL suggests that the tumor microenvironment (TME) contains reversibly exhausted T effector cells (Teffs). However, durable responses are observed in patients with β2-microglobulin/major histocompatibility complex (MHC) class I loss on HRS cells, raising the possibility of non-CD8 + T cell-mediated mechanisms of efficacy of PD-1 blockade. These observations highlight the need for a detailed analysis of the cHL TME. Using a customized time-of-flight mass cytometry panel, we simultaneously assessed cell suspensions from diagnostic cHL biopsies and control reactive lymph node/tonsil (RLNT) samples. Precise phenotyping of immune cell subsets revealed salient differences between cHLs and RLNTs. The TME in cHL is CD4 + T-cell rich, with frequent loss of MHC class I expression on HRS cells. In cHLs, we found concomitant expansion of T helper 1 (Th1)-polarized Teffs and regulatory T cells (Tregs). The cHL Th1 Tregs expressed little or no PD-1, whereas the Th1 Teffs were PD-1 + The differential PD-1 expression and likely functional Th1-polarized CD4 + Tregs and exhausted Teffs may represent complementary mechanisms of immunosuppression in cHL. (© 2018 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2018 Aug 23;132(8):770-771. (PMID: 30139828) |
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| معلومات مُعتمدة: | R01 CA161026 United States CA NCI NIH HHS; U24 CA224316 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20180609 Date Completed: 20190715 Latest Revision: 20210202 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC6107878 |
| DOI: | 10.1182/blood-2018-04-843714 |
| PMID: | 29880615 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2018-04-843714 |