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

Walter Moises Tobias Braga; Bruna Raphaeli da Silva; Ana Carolina de Carvalho; Yumi H Maekawa; Adriana Bruscato Bortoluzzo; Edgar Gil Rizzatti; Djordje Atanackovic; Gisele Wally Braga Colleoni

doi:10.1007/s00262-014-1589-9

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

Standard

FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells. / Braga, Walter Moises Tobias; da Silva, Bruna Raphaeli; de Carvalho, Ana Carolina; Maekawa, Yumi H; Bortoluzzo, Adriana Bruscato; Rizzatti, Edgar Gil; Atanackovic, Djordje; Colleoni, Gisele Wally Braga.

In: CANCER IMMUNOL IMMUN, Vol. 63, No. 11, 2014, p. 1189-97.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Braga, WMT, da Silva, BR, de Carvalho, AC, Maekawa, YH, Bortoluzzo, AB, Rizzatti, EG, Atanackovic, D & Colleoni, GWB 2014, 'FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells', CANCER IMMUNOL IMMUN, vol. 63, no. 11, pp. 1189-97. https://doi.org/10.1007/s00262-014-1589-9

APA

Braga, W. M. T., da Silva, B. R., de Carvalho, A. C., Maekawa, Y. H., Bortoluzzo, A. B., Rizzatti, E. G., Atanackovic, D., & Colleoni, G. W. B. (2014). FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells. CANCER IMMUNOL IMMUN, 63(11), 1189-97. https://doi.org/10.1007/s00262-014-1589-9

Vancouver

Braga WMT, da Silva BR, de Carvalho AC, Maekawa YH, Bortoluzzo AB, Rizzatti EG et al. FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells. CANCER IMMUNOL IMMUN. 2014;63(11):1189-97. https://doi.org/10.1007/s00262-014-1589-9

Bibtex

@article{7880730139ff4e7f9d2cba562d09c23a,

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

abstract = "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.",

keywords = "Adult, Aged, Aged, 80 and over, Biological Markers, Bone Marrow, Bone Marrow Cells, CTLA-4 Antigen, Female, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Humans, Immunosuppression, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Nuclear Receptor Subfamily 1, Group F, Member 3, Plasmacytoma, Syndecan-1, T-Lymphocytes, Regulatory, Th17 Cells, Treatment Outcome",

author = "Braga, {Walter Moises Tobias} and {da Silva}, {Bruna Raphaeli} and {de Carvalho}, {Ana Carolina} and Maekawa, {Yumi H} and Bortoluzzo, {Adriana Bruscato} and Rizzatti, {Edgar Gil} and Djordje Atanackovic and Colleoni, {Gisele Wally Braga}",

year = "2014",

doi = "10.1007/s00262-014-1589-9",

language = "English",

volume = "63",

pages = "1189--97",

journal = "CANCER IMMUNOL IMMUN",

issn = "0340-7004",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "11",

}

RIS

TY - JOUR

T1 - FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4(+) T regulatory cells

AU - Braga, Walter Moises Tobias

AU - da Silva, Bruna Raphaeli

AU - de Carvalho, Ana Carolina

AU - Maekawa, Yumi H

AU - Bortoluzzo, Adriana Bruscato

AU - Rizzatti, Edgar Gil

AU - Atanackovic, Djordje

AU - Colleoni, Gisele Wally Braga

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biological Markers

KW - Bone Marrow

KW - Bone Marrow Cells

KW - CTLA-4 Antigen

KW - Female

KW - Forkhead Transcription Factors

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunosuppression

KW - Male

KW - Middle Aged

KW - Monoclonal Gammopathy of Undetermined Significance

KW - Multiple Myeloma

KW - Nuclear Receptor Subfamily 1, Group F, Member 3

KW - Plasmacytoma

KW - Syndecan-1

KW - T-Lymphocytes, Regulatory

KW - Th17 Cells

KW - Treatment Outcome

U2 - 10.1007/s00262-014-1589-9

DO - 10.1007/s00262-014-1589-9

M3 - SCORING: Journal article

C2 - 25099367

VL - 63

SP - 1189

EP - 1197

JO - CANCER IMMUNOL IMMUN

JF - CANCER IMMUNOL IMMUN

SN - 0340-7004

IS - 11

ER -