FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells
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-h...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | Brasil |
| Institución: | Universidade Federal de São Paulo (UNIFESP) |
| Repositorio: | Repositório Institucional da UNIFESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unifesp.br:11600/38350 |
| Acceso en línea: | http://dx.doi.org/10.1007/s00262-014-1589-9 http://repositorio.unifesp.br/handle/11600/38350 |
| Access Level: | acceso abierto |
| Palabra clave: | Multiple myeloma FOXP3 CTLA4 Treg Therapy |
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FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cellsMultiple myelomaFOXP3CTLA4TregTherapyMultiple 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.Universidade Federal de São Paulo UNIFESP, BR-04037003 São Paulo, BrazilFleury Med & Saude, São Paulo, BrazilInsper Inst Educ & Res, São Paulo, BrazilUniv Med Ctr Hamburg Eppendorf, Hamburg, GermanyUniversidade Federal de São Paulo UNIFESP, BR-04037003 São Paulo, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2010/17668-6SpringerUniversidade Federal de São Paulo (UNIFESP)Fleury Med & SaudeInsper Inst Educ & ResUniv Med Ctr Hamburg Eppendorf2016-01-24T14:38:02Z2016-01-24T14:38:02Z2014-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1189-1197application/pdfhttp://dx.doi.org/10.1007/s00262-014-1589-9Cancer Immunology Immunotherapy. New York: Springer, v. 63, n. 11, p. 1189-1197, 2014.10.1007/s00262-014-1589-9WOS000344324500007.pdf0340-7004http://repositorio.unifesp.br/handle/11600/38350WOS:000344324500007ark:/48912/0013000021j5hengCancer Immunology Immunotherapyinfo:eu-repo/semantics/openAccesshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPTobias Braga, Walter Moises [UNIFESP]Silva, Bruna Raphaeli da [UNIFESP]Carvalho, Ana Carolina de [UNIFESP]Maekawa, Yumi HasegawaBortoluzzo, Adriana BruscatoRizzatti, Edgar GilAtanackovic, DjordjeBraga Colleoni, Gisele Wally [UNIFESP]2024-08-01T06:06:39Zoai:repositorio.unifesp.br:11600/38350Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-01T06:06:39Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.none.fl_str_mv |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| title |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| spellingShingle |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells Tobias Braga, Walter Moises [UNIFESP] Multiple myeloma FOXP3 CTLA4 Treg Therapy |
| title_short |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| title_full |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| title_fullStr |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| title_full_unstemmed |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| title_sort |
FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells |
| dc.creator.none.fl_str_mv |
Tobias Braga, Walter Moises [UNIFESP] Silva, Bruna Raphaeli da [UNIFESP] Carvalho, Ana Carolina de [UNIFESP] Maekawa, Yumi Hasegawa Bortoluzzo, Adriana Bruscato Rizzatti, Edgar Gil Atanackovic, Djordje Braga Colleoni, Gisele Wally [UNIFESP] |
| author |
Tobias Braga, Walter Moises [UNIFESP] |
| author_facet |
Tobias Braga, Walter Moises [UNIFESP] Silva, Bruna Raphaeli da [UNIFESP] Carvalho, Ana Carolina de [UNIFESP] Maekawa, Yumi Hasegawa Bortoluzzo, Adriana Bruscato Rizzatti, Edgar Gil Atanackovic, Djordje Braga Colleoni, Gisele Wally [UNIFESP] |
| author_role |
author |
| author2 |
Silva, Bruna Raphaeli da [UNIFESP] Carvalho, Ana Carolina de [UNIFESP] Maekawa, Yumi Hasegawa Bortoluzzo, Adriana Bruscato Rizzatti, Edgar Gil Atanackovic, Djordje Braga Colleoni, Gisele Wally [UNIFESP] |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Fleury Med & Saude Insper Inst Educ & Res Univ Med Ctr Hamburg Eppendorf |
| dc.subject.por.fl_str_mv |
Multiple myeloma FOXP3 CTLA4 Treg Therapy |
| topic |
Multiple myeloma FOXP3 CTLA4 Treg Therapy |
| description |
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. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014-11-01 2016-01-24T14:38:02Z 2016-01-24T14:38:02Z |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s00262-014-1589-9 Cancer Immunology Immunotherapy. New York: Springer, v. 63, n. 11, p. 1189-1197, 2014. 10.1007/s00262-014-1589-9 WOS000344324500007.pdf 0340-7004 http://repositorio.unifesp.br/handle/11600/38350 WOS:000344324500007 |
| dc.identifier.dark.fl_str_mv |
ark:/48912/0013000021j5h |
| url |
http://dx.doi.org/10.1007/s00262-014-1589-9 http://repositorio.unifesp.br/handle/11600/38350 |
| identifier_str_mv |
Cancer Immunology Immunotherapy. New York: Springer, v. 63, n. 11, p. 1189-1197, 2014. 10.1007/s00262-014-1589-9 WOS000344324500007.pdf 0340-7004 WOS:000344324500007 ark:/48912/0013000021j5h |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Cancer Immunology Immunotherapy |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess http://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0 |
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openAccess |
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http://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0 |
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1189-1197 application/pdf |
| dc.publisher.none.fl_str_mv |
Springer |
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Springer |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
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biblioteca.csp@unifesp.br |
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