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A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts
Cancer-associated fibroblasts (CAFs) are common components of the tumor-suppressive microenvironment, and are a major determinant of the poor outcome of therapeutic vaccination. In this study, we modified tumor cells to express the fibroblast activation protein (FAP), which is highly expressed by CA...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585784/ https://www.ncbi.nlm.nih.gov/pubmed/26394925 http://dx.doi.org/10.1038/srep14421 |
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author | Chen, Meihua Xiang, Rong Wen, Yuan Xu, Guangchao Wang, Chunting Luo, Shuntao Yin, Tao Wei, Xiawei Shao, Bin Liu, Ning Guo, Fuchun Li, Meng Zhang, Shuang Li, Minmin Ren, Kexing Wang, Yongsheng Wei, Yuquan |
author_facet | Chen, Meihua Xiang, Rong Wen, Yuan Xu, Guangchao Wang, Chunting Luo, Shuntao Yin, Tao Wei, Xiawei Shao, Bin Liu, Ning Guo, Fuchun Li, Meng Zhang, Shuang Li, Minmin Ren, Kexing Wang, Yongsheng Wei, Yuquan |
author_sort | Chen, Meihua |
collection | PubMed |
description | Cancer-associated fibroblasts (CAFs) are common components of the tumor-suppressive microenvironment, and are a major determinant of the poor outcome of therapeutic vaccination. In this study, we modified tumor cells to express the fibroblast activation protein (FAP), which is highly expressed by CAFs, to potentially improve whole-cell tumor vaccines by targeting both tumor cells and CAFs. Tumor cells were transfected with murine FAP plasmids bearing the cationic lipid DOTAP. Its antitumor effects were investigated in three established tumor models. Vaccination with tumor cells expressing FAP eliminated solid tumors and tumors resulting from hematogenous dissemination. This antitumor immune response was mediated by CD8+ T cells. Additionally, we found that CAFs were significantly reduced within the tumors. Furthermore, this vaccine enhanced the infiltration of CD8+ T lymphocytes, and suppressed the accumulation of immunosuppressive cells in the tumor microenvironment. Our results indicated that the FAP-modified whole-cell tumor vaccine induced strong antitumor immunity against both tumor cells and CAFs and reversed the immunosuppressive effects of tumors by decreasing the recruitment of immunosuppressive cells and enhancing the recruitment of effector T cells. This conclusion may have important implications for the clinical use of genetically modified tumor cells as cancer vaccines. |
format | Online Article Text |
id | pubmed-4585784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45857842015-09-29 A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts Chen, Meihua Xiang, Rong Wen, Yuan Xu, Guangchao Wang, Chunting Luo, Shuntao Yin, Tao Wei, Xiawei Shao, Bin Liu, Ning Guo, Fuchun Li, Meng Zhang, Shuang Li, Minmin Ren, Kexing Wang, Yongsheng Wei, Yuquan Sci Rep Article Cancer-associated fibroblasts (CAFs) are common components of the tumor-suppressive microenvironment, and are a major determinant of the poor outcome of therapeutic vaccination. In this study, we modified tumor cells to express the fibroblast activation protein (FAP), which is highly expressed by CAFs, to potentially improve whole-cell tumor vaccines by targeting both tumor cells and CAFs. Tumor cells were transfected with murine FAP plasmids bearing the cationic lipid DOTAP. Its antitumor effects were investigated in three established tumor models. Vaccination with tumor cells expressing FAP eliminated solid tumors and tumors resulting from hematogenous dissemination. This antitumor immune response was mediated by CD8+ T cells. Additionally, we found that CAFs were significantly reduced within the tumors. Furthermore, this vaccine enhanced the infiltration of CD8+ T lymphocytes, and suppressed the accumulation of immunosuppressive cells in the tumor microenvironment. Our results indicated that the FAP-modified whole-cell tumor vaccine induced strong antitumor immunity against both tumor cells and CAFs and reversed the immunosuppressive effects of tumors by decreasing the recruitment of immunosuppressive cells and enhancing the recruitment of effector T cells. This conclusion may have important implications for the clinical use of genetically modified tumor cells as cancer vaccines. Nature Publishing Group 2015-09-23 /pmc/articles/PMC4585784/ /pubmed/26394925 http://dx.doi.org/10.1038/srep14421 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chen, Meihua Xiang, Rong Wen, Yuan Xu, Guangchao Wang, Chunting Luo, Shuntao Yin, Tao Wei, Xiawei Shao, Bin Liu, Ning Guo, Fuchun Li, Meng Zhang, Shuang Li, Minmin Ren, Kexing Wang, Yongsheng Wei, Yuquan A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title | A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title_full | A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title_fullStr | A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title_full_unstemmed | A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title_short | A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
title_sort | whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585784/ https://www.ncbi.nlm.nih.gov/pubmed/26394925 http://dx.doi.org/10.1038/srep14421 |
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