Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?

Detalhes bibliográficos
Autor(a) principal: Subramanian, Kritika
Data de Publicação: 2019
Outros Autores: Dierckx, Tim, Khouri, Ricardo, Menezes, Soraya Maria, Kagdi, Huseini, Taylor, Graham P., Farre, Maria de Lourdes, Bittencourt, Achilea Candida Lisboa, Kataoka, Keisuke, Ogawa, Seishi, Van Weyenbergh, Johan
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/36046
Resumo: Conselho Nacional de Desenvolvimento Científico e Tecnológico.
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spelling Subramanian, KritikaDierckx, TimKhouri, RicardoMenezes, Soraya MariaKagdi, HuseiniTaylor, Graham P.Farre, Maria de LourdesBittencourt, Achilea Candida LisboaKataoka, KeisukeOgawa, SeishiVan Weyenbergh, Johan2019-10-01T16:53:20Z2019-10-01T16:53:20Z2019SUBRAMANIAN, Kritika et al. Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: A potential target for immunotherapy? International Journal of Cancer, v. 144, p. 1664-1675, 2019.0020-7136https://www.arca.fiocruz.br/handle/icict/3604610.1002/ijc.31922Conselho Nacional de Desenvolvimento Científico e Tecnológico.2020-01-08St. George’s University School of Medicine. University Centre. Grenada, West Indies / University of Leuven. KU Leuven. Rega Institute for Medical Research, Clinical and Epidemiological Virology. Department of Microbiology and Immunology. Leuven, Belgium.University of Leuven. KU Leuven. Rega Institute for Medical Research, Clinical and Epidemiological Virology. Department of Microbiology and Immunology. Leuven, Belgium.University of Leuven. KU Leuven. Rega Institute for Medical Research, Clinical and Epidemiological Virology. Department of Microbiology and Immunology. Leuven, Belgium / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.University of Leuven. KU Leuven. Rega Institute for Medical Research, Clinical and Epidemiological Virology. Department of Microbiology and Immunology. Leuven, Belgium.Imperial College London. Department of Medicine. London, UK.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Hospital Universitário Prof. Edgard Santos. Salvador, BA, Brasil.Kyoto University. Graduate School of Medicine. Department of Pathology and Tumor Biology. Kyoto, Japan / National Cancer Center Research Institute. Division of Molecular Oncology. Tokyo, Japan.Kyoto University. Graduate School of Medicine. Department of Pathology and Tumor Biology. Kyoto, Japan.University of Leuven. KU Leuven. Rega Institute for Medical Research, Clinical and Epidemiological Virology. Department of Microbiology and Immunology. Leuven, Belgium.Retinoic acid-related drugs have shown promising pre-clinical activity in Adult T-cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we investigated transcriptome-wide interactions of the RORC pathway in HTLV-1 and ATL, using our own and publicly available gene expression data for ATL and other leukemias. Gene expression data from ATL patients were analyzed using WGCNA to determine gene modules and their correlation to clinical and molecular data. Both PBMCs and CD4+ T-Cells exhibited decreased RORC expression in four different ATL cohorts. A small subset of RORChi ATL patients was identified with significantly lower pathognomonic CADM1 and HBZ levels but similar levels of other ATL markers (CD4/CD25/CCR4), hinting at a less aggressive ATL subtype. An age-dependent decrease in RORC expression was found in HTLV-1-infected individuals, but not in healthy controls, suggesting an early molecular event predisposing to leukemogenesis. Genes upstream of RORC signaling were members of a proliferative gene module (containing proliferation markers PCNA/Ki67), whereas downstream members clustered in an anti-proliferative gene module. IL17C transcripts showed the strongest negative correlation to PCNA in both ATL cohorts, which was replicated in two large cohorts of T- and B-cell acute lymphoid leukemia (ALL). Finally, IL17C expression in purified CD4 + CCR4 + CD26-CD7- "ATL-like" cells from HTLV-1-infected individuals and ATL patients was negatively correlated with clonality, underscoring a possible antileukemic/antiproliferative role. In conclusion, decreased RORC expression and downstream signaling might represent an early event in ATL pathogenesis. An antiproliferative IL17C/PCNA link is shared between ATL, T-ALL and B-ALL, suggesting (immuno)therapeutic benefit of boosting RORC/IL17 signaling.engWileyLeucemiaLinfomaProliferaçãoCélulas Th17RetrovírusInflamaçãoImunoterapiaCarcinogênesePCNAIL17CLeukemiaLymphomaProliferationTh17RetrovirusInflammationImmunotherapyCarcinogenesisPCNAIL17CDecreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/36046/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSubramanian, K. Decreased....pdfSubramanian, K. Decreased....pdfapplication/pdf916878https://www.arca.fiocruz.br/bitstream/icict/36046/2/Subramanian%2c%20K.%20Decreased....pdf27fbeffff95f7f1177e8d3870d48bf51MD52TEXTSubramanian, K. Decreased....pdf.txtSubramanian, K. 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dc.title.pt_BR.fl_str_mv Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
title Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
spellingShingle Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
Subramanian, Kritika
Leucemia
Linfoma
Proliferação
Células Th17
Retrovírus
Inflamação
Imunoterapia
Carcinogênese
PCNA
IL17C
Leukemia
Lymphoma
Proliferation
Th17
Retrovirus
Inflammation
Immunotherapy
Carcinogenesis
PCNA
IL17C
title_short Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
title_full Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
title_fullStr Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
title_full_unstemmed Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
title_sort Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: a potential target for immunotherapy?
author Subramanian, Kritika
author_facet Subramanian, Kritika
Dierckx, Tim
Khouri, Ricardo
Menezes, Soraya Maria
Kagdi, Huseini
Taylor, Graham P.
Farre, Maria de Lourdes
Bittencourt, Achilea Candida Lisboa
Kataoka, Keisuke
Ogawa, Seishi
Van Weyenbergh, Johan
author_role author
author2 Dierckx, Tim
Khouri, Ricardo
Menezes, Soraya Maria
Kagdi, Huseini
Taylor, Graham P.
Farre, Maria de Lourdes
Bittencourt, Achilea Candida Lisboa
Kataoka, Keisuke
Ogawa, Seishi
Van Weyenbergh, Johan
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Subramanian, Kritika
Dierckx, Tim
Khouri, Ricardo
Menezes, Soraya Maria
Kagdi, Huseini
Taylor, Graham P.
Farre, Maria de Lourdes
Bittencourt, Achilea Candida Lisboa
Kataoka, Keisuke
Ogawa, Seishi
Van Weyenbergh, Johan
dc.subject.other.pt_BR.fl_str_mv Leucemia
Linfoma
Proliferação
Células Th17
Retrovírus
Inflamação
Imunoterapia
Carcinogênese
PCNA
IL17C
topic Leucemia
Linfoma
Proliferação
Células Th17
Retrovírus
Inflamação
Imunoterapia
Carcinogênese
PCNA
IL17C
Leukemia
Lymphoma
Proliferation
Th17
Retrovirus
Inflammation
Immunotherapy
Carcinogenesis
PCNA
IL17C
dc.subject.en.pt_BR.fl_str_mv Leukemia
Lymphoma
Proliferation
Th17
Retrovirus
Inflammation
Immunotherapy
Carcinogenesis
PCNA
IL17C
description Conselho Nacional de Desenvolvimento Científico e Tecnológico.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-10-01T16:53:20Z
dc.date.available.fl_str_mv 2019-10-01T16:53:20Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SUBRAMANIAN, Kritika et al. Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: A potential target for immunotherapy? International Journal of Cancer, v. 144, p. 1664-1675, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/36046
dc.identifier.issn.pt_BR.fl_str_mv 0020-7136
dc.identifier.doi.none.fl_str_mv 10.1002/ijc.31922
identifier_str_mv SUBRAMANIAN, Kritika et al. Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: A potential target for immunotherapy? International Journal of Cancer, v. 144, p. 1664-1675, 2019.
0020-7136
10.1002/ijc.31922
url https://www.arca.fiocruz.br/handle/icict/36046
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/36046/3/Subramanian%2c%20K.%20Decreased....pdf.txt
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