Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells
| Autor: | Sameena Iqbal, John G. Gribben, Maria Calaminici, Paul Greaves, Abigail M. Lee, Andrew Wilson, Janet Matthews, Andrew Clear, Andrew Owen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Adolescent CD30 Immunology Biochemistry Immunophenotyping Flow cytometry Young Adult immune system diseases Aldesleukin hemic and lymphatic diseases Tumor Microenvironment Humans Medicine Cellular Senescence Interleukin 4 Aged Cell Proliferation Tumor microenvironment Lymphoid Neoplasia medicine.diagnostic_test business.industry T-Lymphocytes Helper-Inducer Cell Biology Hematology Middle Aged Flow Cytometry Hodgkin Disease Immunohistochemistry Treatment Outcome Interleukin 13 Cancer research Cytokines Female Cytokine secretion business Immunosuppressive Agents |
| Zdroj: | Blood. 122:2856-2863 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-06-508044 |
| Popis: | CD4(+) T-helper cells (THs) dominate the classical Hodgkin lymphoma (CHL) microenvironment, but their role is poorly understood. Advances in flow cytometry and immunohistochemistry permit more detailed investigation of this aspect of CHL pathophysiology. To address the hypothesis that the TH-infiltrate, rather than being TH2-enriched, senescent and hypofunctional, is TH1 and activation marker-rich, cytokine-secretory and proliferative, we applied comprehensive flow cytometric immunophenotyping and functional assays of cytokine secretion/proliferation to TH cells from 18 CHL-derived single-cell suspensions (SCSs) compared to reactive lymph nodes (RLNs). CHL-derived TH cells express TH1-associated CXCR3/CCR5 and TNFα/IFNγ/interleukin-2 (IL-2) and less TH2-associated CCR3/CCR4, with no IL-4/IL-13. They lack exhaustion-/suppression-associated PD1, CD57 and terminally differentiated effector memory cells, with more central memory cells, activation-associated partners of Hodgkin Reed Sternberg (HRS) cell-expressed CD30/OX40-L/ICOS-L, and other activation markers. TH cell lines established from CHL and RLN-derived SCSs remain cytokine-secretory. We confirmed and extended these studies using tissue microarray immunohistochemistry (TMA-IHC) from a large CHL tissue bank (n = 122) and demonstrate TH1-associated TBET is abundant in CHL, and TH2-associated CMAF/GATA3 and exhaustion-associated PD1 expressed at significantly lower levels. These molecular insights into the CHL-associated TH offer potential diagnostic, prognostic and pharmacologically modifiable therapeutic targets and do not support the established view of a TH2-enriched, senescent/exhausted, hypofunctional, hypoproliferative infiltrate. |
| Databáze: | OpenAIRE |
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