HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy

Abstract Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical im...

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Autores principales:	María Belén Palma, Diana Tronik-Le Roux, Guadalupe Amín, Sheila Castañeda, Alan M. Möbbs, María Agustina Scarafia, Alejandro La Greca, Marina Daouya, Isabelle Poras, Ana María Inda, Lucía N. Moro, Edgardo D. Carosella, Marcela N. García, Santiago G. Miriuka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/894a26ff5d8c49e7b84811e2e58054c0
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spelling	oai:doaj.org-article:894a26ff5d8c49e7b84811e2e58054c02021-11-14T12:20:40ZHLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy10.1038/s41598-021-01572-02045-2322https://doaj.org/article/894a26ff5d8c49e7b84811e2e58054c02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01572-0https://doaj.org/toc/2045-2322Abstract Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G − cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.María Belén PalmaDiana Tronik-Le RouxGuadalupe AmínSheila CastañedaAlan M. MöbbsMaría Agustina ScarafiaAlejandro La GrecaMarina DaouyaIsabelle PorasAna María IndaLucía N. MoroEdgardo D. CarosellaMarcela N. GarcíaSantiago G. MiriukaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María Belén Palma Diana Tronik-Le Roux Guadalupe Amín Sheila Castañeda Alan M. Möbbs María Agustina Scarafia Alejandro La Greca Marina Daouya Isabelle Poras Ana María Inda Lucía N. Moro Edgardo D. Carosella Marcela N. García Santiago G. Miriuka HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
description	Abstract Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G − cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.
format	article
author	María Belén Palma Diana Tronik-Le Roux Guadalupe Amín Sheila Castañeda Alan M. Möbbs María Agustina Scarafia Alejandro La Greca Marina Daouya Isabelle Poras Ana María Inda Lucía N. Moro Edgardo D. Carosella Marcela N. García Santiago G. Miriuka
author_facet	María Belén Palma Diana Tronik-Le Roux Guadalupe Amín Sheila Castañeda Alan M. Möbbs María Agustina Scarafia Alejandro La Greca Marina Daouya Isabelle Poras Ana María Inda Lucía N. Moro Edgardo D. Carosella Marcela N. García Santiago G. Miriuka
author_sort	María Belén Palma
title	HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
title_short	HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
title_full	HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
title_fullStr	HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
title_full_unstemmed	HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
title_sort	hla-g gene editing in tumor cell lines as a novel alternative in cancer immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/894a26ff5d8c49e7b84811e2e58054c0
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HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy

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