FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells

Autor(es)

Tobias Braga, Walter Moises ^[1] ; da Silva, Bruna Raphaeli ^[1] ; de Carvalho, Ana Carolina ^[1] ; Maekawa, Yumi H. ^[2] ; Bortoluzzo, Adriana Bruscato ^[3] ; Rizzatti, Edgar Gil ^[2] ; Atanackovic, Djordje ^[4] ; Braga Colleoni, Gisele Wally ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, BR-04037003 Sao Paulo - Brazil

^[2] Fleury Med & Saude, Sao Paulo - Brazil

^[3] Insper Inst Educ & Res, Sao Paulo - Brazil

^[4] Univ Med Ctr Hamburg Eppendorf, Hamburg - Germany

• Tipo de documento: Artigo Científico
• Fonte: CANCER IMMUNOLOGY IMMUNOTHERAPY; v. 63, n. 11, p. 1189-1197, NOV 2014.
• Citações Web of Science: 29

Resumo

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. Expression of markers for Treg (FOXP3, CTLA4) and Th17 cells (ROR gamma t) 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). FOXP3 and CTLA4 presented a sixfold (p = 0.02) and 30-fold higher expression (p = 0.03), respectively, in MM patients than in controls. ROR gamma t 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. 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. (AU)

• Processo FAPESP: 10/17668-6 - Identificação de marcadores tumorais e possíveis alvos terapêuticos em doenças linfoproliferativas de células B
• Beneficiário: Gisele Wally Braga Colleoni
• Modalidade de apoio: Auxílio à Pesquisa - Temático