SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma

Autores
Chen, Xuemei; Kunda, Patricia Elena; Lin, Jianwei; Zhou, Meiling; Huang, Jinghan; Zhang, Huqin; Liu, Tao
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.
Fil: Chen, Xuemei. Xi'an Jiaotong University; China
Fil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Lin, Jianwei. Shenzhen University; China
Fil: Zhou, Meiling. Shenzhen Luohu Peoples Hospital; China. Shenzhen University; China
Fil: Huang, Jinghan. Shenzhen Luohu Peoples Hospital; China
Fil: Zhang, Huqin. Xi'an Jiaotong University; China
Fil: Liu, Tao. Shenzhen University; China. Shenzhen Luohu Peoples Hospital; China
Materia
AUTOLOGOUS ADOPTIVE IMMUNOTHERAPY
CYTOTOXIC T LYMPHOCYTES
DENDRITIC CELLS
RETINOBLASTOMA
SPLEEN TYROSINE KINASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/89362
Acceder
id CONICETDig_cb518052920b4d869113f5e5bebde685
oai_identifier_str oai:ri.conicet.gov.ar:11336/89362
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastomaChen, XuemeiKunda, Patricia ElenaLin, JianweiZhou, MeilingHuang, JinghanZhang, HuqinLiu, TaoAUTOLOGOUS ADOPTIVE IMMUNOTHERAPYCYTOTOXIC T LYMPHOCYTESDENDRITIC CELLSRETINOBLASTOMASPLEEN TYROSINE KINASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.Fil: Chen, Xuemei. Xi'an Jiaotong University; ChinaFil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lin, Jianwei. Shenzhen University; ChinaFil: Zhou, Meiling. Shenzhen Luohu Peoples Hospital; China. Shenzhen University; ChinaFil: Huang, Jinghan. Shenzhen Luohu Peoples Hospital; ChinaFil: Zhang, Huqin. Xi'an Jiaotong University; ChinaFil: Liu, Tao. Shenzhen University; China. Shenzhen Luohu Peoples Hospital; ChinaSpringer2018-01-25info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89362Chen, Xuemei; Kunda, Patricia Elena; Lin, Jianwei; Zhou, Meiling; Huang, Jinghan; et al.; SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma; Springer; Journal Of Cancer Research And Clinical Oncology; 144; 4; 25-1-2018; 675-6840171-52161432-1335CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00432-018-2584-xinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00432-018-2584-xinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/29372378info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:21Zoai:ri.conicet.gov.ar:11336/89362instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:10:21.786CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
title SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
spellingShingle SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
Chen, Xuemei
AUTOLOGOUS ADOPTIVE IMMUNOTHERAPY
CYTOTOXIC T LYMPHOCYTES
DENDRITIC CELLS
RETINOBLASTOMA
SPLEEN TYROSINE KINASE
title_short SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
title_full SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
title_fullStr SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
title_full_unstemmed SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
title_sort SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma
dc.creator.none.fl_str_mv Chen, Xuemei
Kunda, Patricia Elena
Lin, Jianwei
Zhou, Meiling
Huang, Jinghan
Zhang, Huqin
Liu, Tao
author Chen, Xuemei
author_facet Chen, Xuemei
Kunda, Patricia Elena
Lin, Jianwei
Zhou, Meiling
Huang, Jinghan
Zhang, Huqin
Liu, Tao
author_role author
author2 Kunda, Patricia Elena
Lin, Jianwei
Zhou, Meiling
Huang, Jinghan
Zhang, Huqin
Liu, Tao
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOLOGOUS ADOPTIVE IMMUNOTHERAPY
CYTOTOXIC T LYMPHOCYTES
DENDRITIC CELLS
RETINOBLASTOMA
SPLEEN TYROSINE KINASE
topic AUTOLOGOUS ADOPTIVE IMMUNOTHERAPY
CYTOTOXIC T LYMPHOCYTES
DENDRITIC CELLS
RETINOBLASTOMA
SPLEEN TYROSINE KINASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.
Fil: Chen, Xuemei. Xi'an Jiaotong University; China
Fil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Lin, Jianwei. Shenzhen University; China
Fil: Zhou, Meiling. Shenzhen Luohu Peoples Hospital; China. Shenzhen University; China
Fil: Huang, Jinghan. Shenzhen Luohu Peoples Hospital; China
Fil: Zhang, Huqin. Xi'an Jiaotong University; China
Fil: Liu, Tao. Shenzhen University; China. Shenzhen Luohu Peoples Hospital; China
description Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.
publishDate 2018
dc.date.none.fl_str_mv 2018-01-25
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/89362
Chen, Xuemei; Kunda, Patricia Elena; Lin, Jianwei; Zhou, Meiling; Huang, Jinghan; et al.; SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma; Springer; Journal Of Cancer Research And Clinical Oncology; 144; 4; 25-1-2018; 675-684
0171-5216
1432-1335
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89362
identifier_str_mv Chen, Xuemei; Kunda, Patricia Elena; Lin, Jianwei; Zhou, Meiling; Huang, Jinghan; et al.; SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma; Springer; Journal Of Cancer Research And Clinical Oncology; 144; 4; 25-1-2018; 675-684
0171-5216
1432-1335
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00432-018-2584-x
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00432-018-2584-x
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/29372378
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613991604682752
score 13.070432

Publicaciones similares