A germinal center–associated microenvironmental signature reflects malignant phenotype and outcome of DLBCL
| Autor: | Takeshi Sugio, Kensuke Sasaki, Jon C. Aster, Toshihiro Miyamoto, Koichi Akashi, Yuichiro Semba, Hiroaki Miyoshi, Yuya Kunisaki, Hiromi Iwasaki, Yasuo Mori, Takahiro Maeda, Koji Kato, Yoshikane Kikushige, Kohta Miyawaki, Frank C. Kuo, Koichi Ohshima |
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| Rok vydání: | 2022 |
| Předmět: |
Vincristine
Stromal cell Malignancy Stem cell marker immune system diseases hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols Tumor Microenvironment medicine Humans Cyclophosphamide business.industry Germinal center Hematology Germinal Center medicine.disease Lymphoma Gene expression profiling Phenotype Doxorubicin Cancer research Prednisone Rituximab Lymphoma Large B-Cell Diffuse business medicine.drug |
| Zdroj: | Blood Advances. 6:2388-2402 |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy, with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves, including cell-of-origin (COO), genomic alterations, and gene/protein expressions. However, the prognostic impact of the lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using the nCounter-based gene expression profiling of untreated DLBCL tissues, we assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures. |
| Databáze: | OpenAIRE |
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