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; 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

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.

Metadados do item

id	CRUZ_b3cb4d75332717909cbdd068edb36a66
oai_identifier_str	oai:www.arca.fiocruz.br:icict/36046
network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
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. Decreased....pdf.txtExtracted texttext/plain52641https://www.arca.fiocruz.br/bitstream/icict/36046/3/Subramanian%2c%20K.%20Decreased....pdf.txt8fa67a074ed4385e80df3a06e5123fe5MD53icict/360462023-03-15 14:34:21.867oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:21Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
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)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/36046/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/36046/2/Subramanian%2c%20K.%20Decreased....pdf https://www.arca.fiocruz.br/bitstream/icict/36046/3/Subramanian%2c%20K.%20Decreased....pdf.txt
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repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
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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?

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