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Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells
METHODS: We analyzed the secretion of cytokines, chemokines, and growth factors in 22Rv1, LNCaP, and DU145 cells. In these cells, we also evaluated the expression of NK ligands, IL6R, STAT-3, and phosporylated STAT-3. In NK-92 cells, we evaluated the effects of Stattic (Stt) and tocilizumab (Tcz) on...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020142/ https://www.ncbi.nlm.nih.gov/pubmed/35465350 http://dx.doi.org/10.1155/2022/1810804 |
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author | González-Ochoa, S. Tellez-Bañuelos, M. C. Méndez-Clemente, A. S. Bravo-Cuellar, A. Hernández Flores, G. Palafox-Mariscal, L. A. Haramati, J. Pedraza-Brindis, E. J. Sánchez-Reyes, K. Ortiz-Lazareno, P. C. |
author_facet | González-Ochoa, S. Tellez-Bañuelos, M. C. Méndez-Clemente, A. S. Bravo-Cuellar, A. Hernández Flores, G. Palafox-Mariscal, L. A. Haramati, J. Pedraza-Brindis, E. J. Sánchez-Reyes, K. Ortiz-Lazareno, P. C. |
author_sort | González-Ochoa, S. |
collection | PubMed |
description | METHODS: We analyzed the secretion of cytokines, chemokines, and growth factors in 22Rv1, LNCaP, and DU145 cells. In these cells, we also evaluated the expression of NK ligands, IL6R, STAT-3, and phosporylated STAT-3. In NK-92 cells, we evaluated the effects of Stattic (Stt) and tocilizumab (Tcz) on NK receptors. In addition, we assessed if the disruption of the IL6R/STAT-3 pathway and blockade of TIGIT potentiated the cytotoxicity of NK-92 cells versus DU145 cells. RESULTS: DU145 abundantly secretes M-CSF, VEGF, IL-6, CXCL8, and TGF-β. Furthermore, the expression of CD155 was found to increase in accordance with aggressiveness and metastatic status in the prostate cancer cells. Stt and Tcz induce a decrease in STAT-3 phosphorylation in the DU145 cells and, in turn, induce an increase of NKp46 and a decrease of TIGIT expression in NK-92 cells. Finally, the disruption of the IL6R/STAT-3 axis in prostate cancer cells and the blocking of TIGIT on NK-92 were observed to increase the cytotoxicity of NK-92 cells against DU145 cells through an increase in sFasL, granzyme A, granzyme B, and granulysin. CONCLUSIONS: Our results reveal that the combined use of inhibitors directed against the IL6R/STAT-3 axis and TIGIT enhances the functional activity of NK cells against castration-resistant prostate cancer cells. |
format | Online Article Text |
id | pubmed-9020142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-90201422022-04-21 Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells González-Ochoa, S. Tellez-Bañuelos, M. C. Méndez-Clemente, A. S. Bravo-Cuellar, A. Hernández Flores, G. Palafox-Mariscal, L. A. Haramati, J. Pedraza-Brindis, E. J. Sánchez-Reyes, K. Ortiz-Lazareno, P. C. J Immunol Res Research Article METHODS: We analyzed the secretion of cytokines, chemokines, and growth factors in 22Rv1, LNCaP, and DU145 cells. In these cells, we also evaluated the expression of NK ligands, IL6R, STAT-3, and phosporylated STAT-3. In NK-92 cells, we evaluated the effects of Stattic (Stt) and tocilizumab (Tcz) on NK receptors. In addition, we assessed if the disruption of the IL6R/STAT-3 pathway and blockade of TIGIT potentiated the cytotoxicity of NK-92 cells versus DU145 cells. RESULTS: DU145 abundantly secretes M-CSF, VEGF, IL-6, CXCL8, and TGF-β. Furthermore, the expression of CD155 was found to increase in accordance with aggressiveness and metastatic status in the prostate cancer cells. Stt and Tcz induce a decrease in STAT-3 phosphorylation in the DU145 cells and, in turn, induce an increase of NKp46 and a decrease of TIGIT expression in NK-92 cells. Finally, the disruption of the IL6R/STAT-3 axis in prostate cancer cells and the blocking of TIGIT on NK-92 were observed to increase the cytotoxicity of NK-92 cells against DU145 cells through an increase in sFasL, granzyme A, granzyme B, and granulysin. CONCLUSIONS: Our results reveal that the combined use of inhibitors directed against the IL6R/STAT-3 axis and TIGIT enhances the functional activity of NK cells against castration-resistant prostate cancer cells. Hindawi 2022-04-12 /pmc/articles/PMC9020142/ /pubmed/35465350 http://dx.doi.org/10.1155/2022/1810804 Text en Copyright © 2022 S. González-Ochoa et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article González-Ochoa, S. Tellez-Bañuelos, M. C. Méndez-Clemente, A. S. Bravo-Cuellar, A. Hernández Flores, G. Palafox-Mariscal, L. A. Haramati, J. Pedraza-Brindis, E. J. Sánchez-Reyes, K. Ortiz-Lazareno, P. C. Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title | Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title_full | Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title_fullStr | Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title_full_unstemmed | Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title_short | Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells |
title_sort | combination blockade of the il6r/stat-3 axis with tigit and its impact on the functional activity of nk cells against prostate cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020142/ https://www.ncbi.nlm.nih.gov/pubmed/35465350 http://dx.doi.org/10.1155/2022/1810804 |
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