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

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

Author Tobias Braga, Walter Moises Autor UNIFESP Google Scholar
Silva, Bruna Raphaeli da Autor UNIFESP Google Scholar
Carvalho, Ana Carolina de Autor UNIFESP Google Scholar
Maekawa, Yumi Hasegawa Google Scholar
Bortoluzzo, Adriana Bruscato Google Scholar
Rizzatti, Edgar Gil Google Scholar
Atanackovic, Djordje Google Scholar
Braga Colleoni, Gisele Wally Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Fleury Med & Saude
Insper Inst Educ & Res
Univ Med Ctr Hamburg Eppendorf
Abstract 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.
Keywords Multiple myeloma
FOXP3
CTLA4
Treg
Therapy
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2010/17668-6
Date 2014-11-01
Published in Cancer Immunology Immunotherapy. New York: Springer, v. 63, n. 11, p. 1189-1197, 2014.
ISSN 0340-7004 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 1189-1197
Origin http://dx.doi.org/10.1007/s00262-014-1589-9
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000344324500007
URI http://repositorio.unifesp.br/handle/11600/38350

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