FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells
| Autor: | Yumi H. Maekawa, Adriana Bruscato Bortoluzzo, Bruna Raphaeli Silva, Ana Carolina de Carvalho, Gisele W. B. Colleoni, Edgar Gil Rizzatti, Walter Moises Tobias Braga, Djordje Atanackovic |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Cancer Research FOXP3 medicine.medical_treatment Immunology chemical and pharmacologic phenomena Bone Marrow Cells Biology Monoclonal Gammopathy of Undetermined Significance T-Lymphocytes Regulatory Syndecan 1 Immune system Bone Marrow Multiple myeloma medicine Immunology and Allergy Humans CTLA-4 Antigen Aged Aged 80 and over Immunosuppression Therapy CTLA4 Immunosuppression Forkhead Transcription Factors Middle Aged Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Gene Expression Regulation Neoplastic Treg medicine.anatomical_structure Treatment Outcome Oncology Plasmacytoma Th17 Cells Female Original Article Bone marrow Syndecan-1 Therapy Monoclonal gammopathy of undetermined significance Biomarkers |
| Zdroj: | Cancer Immunology, Immunotherapy |
| ISSN: | 1432-0851 |
| Popis: | Introduction Multiple myeloma (MM) development involves a series of genetic abnormalities and changes in the bone marrow (BM) microenvironment, favoring the growth of the tumor and failure of local immune control. T regulatory (Treg) cells play an important role in dampening anti-tumor immune responses while T-helper-17 (Th17) cells seem to be critical for the eradication of malignant cells. The aim of our study was to characterize the expression of Treg- and Th17-related genes in total myeloma BM samples to assess their role as biomarkers, prognostic factors, and possible therapeutic targets in this incurable disease. Methods Expression of markers for Treg (FOXP3, CTLA4) and Th17 cells (RORγt) was determined by quantitative real-time PCR in BM aspirates of 46 MM patients, four patients with monoclonal gammopathy of undetermined significance, five solitary plasmacytomas, and five healthy BM donors. Gene expression was evaluated regarding an influence on the patients’ overall survival (OS). Results FOXP3 and CTLA4 presented a sixfold (p = 0.02) and 30-fold higher expression (p = 0.03), respectively, in MM patients than in controls. RORγt expression was similar in MM patients and controls. Median OS of MM patients was 16.8 (range 4.5–29.1) months, and international staging system was the only independent prognostic factor for patients survival. Conclusions Overexpression of FOXP3 and CTLA4 in total BM samples suggests a local accumulation of immunosuppressive Tregs, the MM tumor environment, possibly dampening anti-tumor host immune responses. Therapeutic approaches targeting Treg cells and restoring local anti-tumor immunity may provide new treatment strategies for this incurable malignancy. Electronic supplementary material The online version of this article (doi:10.1007/s00262-014-1589-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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