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Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma

There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our...

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Autores principales: Hong, Shanjuan, Yuan, Qing, Xia, Haizhui, Dou, Yuan, Sun, Tiantian, Xie, Tian, Zhang, Zhiyin, He, Wei, Dong, Chen, Lu, Jian, Guo, Li, Ni, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019348/
https://www.ncbi.nlm.nih.gov/pubmed/35463322
http://dx.doi.org/10.3389/fonc.2022.851191
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author Hong, Shanjuan
Yuan, Qing
Xia, Haizhui
Dou, Yuan
Sun, Tiantian
Xie, Tian
Zhang, Zhiyin
He, Wei
Dong, Chen
Lu, Jian
Guo, Li
Ni, Ling
author_facet Hong, Shanjuan
Yuan, Qing
Xia, Haizhui
Dou, Yuan
Sun, Tiantian
Xie, Tian
Zhang, Zhiyin
He, Wei
Dong, Chen
Lu, Jian
Guo, Li
Ni, Ling
author_sort Hong, Shanjuan
collection PubMed
description There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this ex vivo tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC.
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spelling pubmed-90193482022-04-21 Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma Hong, Shanjuan Yuan, Qing Xia, Haizhui Dou, Yuan Sun, Tiantian Xie, Tian Zhang, Zhiyin He, Wei Dong, Chen Lu, Jian Guo, Li Ni, Ling Front Oncol Oncology There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this ex vivo tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9019348/ /pubmed/35463322 http://dx.doi.org/10.3389/fonc.2022.851191 Text en Copyright © 2022 Hong, Yuan, Xia, Dou, Sun, Xie, Zhang, He, Dong, Lu, Guo and Ni https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hong, Shanjuan
Yuan, Qing
Xia, Haizhui
Dou, Yuan
Sun, Tiantian
Xie, Tian
Zhang, Zhiyin
He, Wei
Dong, Chen
Lu, Jian
Guo, Li
Ni, Ling
Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title_full Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title_fullStr Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title_short Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
title_sort establishment of an ex vivo tissue culture model for evaluation of antitumor efficacy in clear cell renal cell carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019348/
https://www.ncbi.nlm.nih.gov/pubmed/35463322
http://dx.doi.org/10.3389/fonc.2022.851191
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