Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing

Abstract Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune s...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yi-Hsin Liang, Jia-Huei Tsai, Yung-Ming Cheng, Kuang-Yu Chan, Wen-Ling Hsu, Chang-Cheng Lee, Kuo-Hsing Chen, Kun-Huei Yeh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/850bbe547505437589968e4bfba8bd88
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:850bbe547505437589968e4bfba8bd88
record_format	dspace
spelling	oai:doaj.org-article:850bbe547505437589968e4bfba8bd882021-12-02T17:39:20ZChemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing10.1038/s41598-021-88648-z2045-2322https://doaj.org/article/850bbe547505437589968e4bfba8bd882021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88648-zhttps://doaj.org/toc/2045-2322Abstract Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.Yi-Hsin LiangJia-Huei TsaiYung-Ming ChengKuang-Yu ChanWen-Ling HsuChang-Cheng LeeKuo-Hsing ChenKun-Huei YehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi-Hsin Liang Jia-Huei Tsai Yung-Ming Cheng Kuang-Yu Chan Wen-Ling Hsu Chang-Cheng Lee Kuo-Hsing Chen Kun-Huei Yeh Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
description	Abstract Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.
format	article
author	Yi-Hsin Liang Jia-Huei Tsai Yung-Ming Cheng Kuang-Yu Chan Wen-Ling Hsu Chang-Cheng Lee Kuo-Hsing Chen Kun-Huei Yeh
author_facet	Yi-Hsin Liang Jia-Huei Tsai Yung-Ming Cheng Kuang-Yu Chan Wen-Ling Hsu Chang-Cheng Lee Kuo-Hsing Chen Kun-Huei Yeh
author_sort	Yi-Hsin Liang
title	Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
title_short	Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
title_full	Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
title_fullStr	Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
title_full_unstemmed	Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
title_sort	chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/850bbe547505437589968e4bfba8bd88
work_keys_str_mv	AT yihsinliang chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT jiahueitsai chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT yungmingcheng chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT kuangyuchan chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT wenlinghsu chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT changchenglee chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT kuohsingchen chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing AT kunhueiyeh chemotherapyagentsstimulatedendriticcellsagainsthumancoloncancercellsthroughupregulationofthetransporterassociatedwithantigenprocessing
_version_	1718379832801230848

Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing

Ejemplares similares