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Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer
Interferon-γ (IFNγ) is a cytokine with limited evidence of benefit in cancer clinical trials to date. However, it could potentially play a role in potentiating anti-tumor immunity in the immunologically "cold" metastatic castration-resistant prostate cancer (mCRPC) by inducing antigen pres...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033763/ https://www.ncbi.nlm.nih.gov/pubmed/35459800 http://dx.doi.org/10.1038/s41598-022-10724-9 |
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author | Korentzelos, Dimitrios Wells, Alan Clark, Amanda M. |
author_facet | Korentzelos, Dimitrios Wells, Alan Clark, Amanda M. |
author_sort | Korentzelos, Dimitrios |
collection | PubMed |
description | Interferon-γ (IFNγ) is a cytokine with limited evidence of benefit in cancer clinical trials to date. However, it could potentially play a role in potentiating anti-tumor immunity in the immunologically "cold" metastatic castration-resistant prostate cancer (mCRPC) by inducing antigen presentation pathways and concurrently providing targets for immune checkpoint blockade therapy. Moreover, it could additionally increase sensitivity to chemotherapy based on its pleiotropic effects on cell phenotype. Here, we show that IFNγ treatment induced expression of major histocompatibility class-I (MHC-I) genes and PD-L1 in prostate cancer cells in vitro. Furthermore, IFNγ treatment led to a decrease in E-cadherin expression with a consequent increase in sensitivity to chemotherapy in vitro. In an in vivo murine tumor model of spontaneous metastatic prostate cancer, IFNγ systemic pretreatment upregulated the expression of HLA-A and decreased E-cadherin expression in the primary tumor, and more importantly in the metastatic site led to increased apoptosis and limited micrometastases in combination with paclitaxel treatment compared to diffuse metastatic disease in control and monotherapy treatment groups. These findings suggest that IFNγ may be useful in combinatorial regimens to induce sensitivity to immunotherapy and chemotherapy in hepatic metastases of mCRPC. |
format | Online Article Text |
id | pubmed-9033763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90337632022-04-25 Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer Korentzelos, Dimitrios Wells, Alan Clark, Amanda M. Sci Rep Article Interferon-γ (IFNγ) is a cytokine with limited evidence of benefit in cancer clinical trials to date. However, it could potentially play a role in potentiating anti-tumor immunity in the immunologically "cold" metastatic castration-resistant prostate cancer (mCRPC) by inducing antigen presentation pathways and concurrently providing targets for immune checkpoint blockade therapy. Moreover, it could additionally increase sensitivity to chemotherapy based on its pleiotropic effects on cell phenotype. Here, we show that IFNγ treatment induced expression of major histocompatibility class-I (MHC-I) genes and PD-L1 in prostate cancer cells in vitro. Furthermore, IFNγ treatment led to a decrease in E-cadherin expression with a consequent increase in sensitivity to chemotherapy in vitro. In an in vivo murine tumor model of spontaneous metastatic prostate cancer, IFNγ systemic pretreatment upregulated the expression of HLA-A and decreased E-cadherin expression in the primary tumor, and more importantly in the metastatic site led to increased apoptosis and limited micrometastases in combination with paclitaxel treatment compared to diffuse metastatic disease in control and monotherapy treatment groups. These findings suggest that IFNγ may be useful in combinatorial regimens to induce sensitivity to immunotherapy and chemotherapy in hepatic metastases of mCRPC. Nature Publishing Group UK 2022-04-22 /pmc/articles/PMC9033763/ /pubmed/35459800 http://dx.doi.org/10.1038/s41598-022-10724-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Korentzelos, Dimitrios Wells, Alan Clark, Amanda M. Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title | Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title_full | Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title_fullStr | Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title_full_unstemmed | Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title_short | Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
title_sort | interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033763/ https://www.ncbi.nlm.nih.gov/pubmed/35459800 http://dx.doi.org/10.1038/s41598-022-10724-9 |
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