Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
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
_version_ 1782392275836338176
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
work_keys_str_mv AT chenmeihua awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT xiangrong awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wenyuan awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT xuguangchao awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wangchunting awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT luoshuntao awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT yintao awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT weixiawei awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT shaobin awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT liuning awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT guofuchun awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT limeng awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT zhangshuang awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT liminmin awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT renkexing awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wangyongsheng awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT weiyuquan awholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT chenmeihua wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT xiangrong wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wenyuan wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT xuguangchao wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wangchunting wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT luoshuntao wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT yintao wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT weixiawei wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT shaobin wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT liuning wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT guofuchun wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT limeng wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT zhangshuang wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT liminmin wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT renkexing wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT wangyongsheng wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts
AT weiyuquan wholecelltumorvaccinemodifiedtoexpressfibroblastactivationproteininducesantitumorimmunityagainstbothtumorcellsandcancerassociatedfibroblasts