In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts
T cell immunotherapy is now a mainstay therapy for several blood-borne cancers as well as metastatic melanoma. Unfortunately, many epithelial tumors respond poorly to immunotherapy, and the reasons for this are not well understood. Cancer-associated fibroblasts (CAFs) are the most frequent non-neopl...
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doaj-6c39f43aee254ac69e53581d6f5242fe2021-02-13T00:02:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01221827182710.3390/ijms22041827In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated FibroblastsMohammed H. Abuwarwar0Alfie T. Baker1Jeffrey Harding2Natalie L. Payne3Andras Nagy4Konstantin Knoblich5Anne L. Fletcher6Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, AustraliaBiomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, AustraliaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, CanadaAustralian Regenerative Medicine Institute, Monash University, Clayton 3800, AustraliaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, CanadaBiomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, AustraliaBiomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, AustraliaT cell immunotherapy is now a mainstay therapy for several blood-borne cancers as well as metastatic melanoma. Unfortunately, many epithelial tumors respond poorly to immunotherapy, and the reasons for this are not well understood. Cancer-associated fibroblasts (CAFs) are the most frequent non-neoplastic cell type in most solid tumors, and they are emerging as a key player in immunotherapy resistance. A range of immortalized CAF lines will be essential tools that will allow us to understand immune responses against cancer and develop novel strategies for cancer immunotherapy. To study the effect of CAFs on T cell proliferation, we created and characterized a number of novel immortalized human CAFs lines (Im-CAFs) from human breast, colon, and pancreatic carcinomas. Im-CAFs shared similar phenotypes, matrix remodeling and contraction capabilities, and growth and migration rates compared to the primary CAFs. Using primary isolates from breast carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma, we report that CAFs across major tumor types are able to potently suppress T cell proliferation in vitro. Im-CAFs retained this property. Im-CAFs are a key tool that will provide important insights into the mechanisms of CAF-mediated T cell suppression through techniques such as CRISPR-Cas9 modification, molecular screens, and pipeline drug testing.https://www.mdpi.com/1422-0067/22/4/1827Stromal cellsT cellscancer-associated fibroblaststumor microenvironmenttumor immunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mohammed H. Abuwarwar Alfie T. Baker Jeffrey Harding Natalie L. Payne Andras Nagy Konstantin Knoblich Anne L. Fletcher |
spellingShingle |
Mohammed H. Abuwarwar Alfie T. Baker Jeffrey Harding Natalie L. Payne Andras Nagy Konstantin Knoblich Anne L. Fletcher In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts International Journal of Molecular Sciences Stromal cells T cells cancer-associated fibroblasts tumor microenvironment tumor immunology |
author_facet |
Mohammed H. Abuwarwar Alfie T. Baker Jeffrey Harding Natalie L. Payne Andras Nagy Konstantin Knoblich Anne L. Fletcher |
author_sort |
Mohammed H. Abuwarwar |
title |
In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts |
title_short |
In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts |
title_full |
In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts |
title_fullStr |
In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts |
title_full_unstemmed |
In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts |
title_sort |
in vitro suppression of t cell proliferation is a conserved function of primary and immortalized human cancer-associated fibroblasts |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-02-01 |
description |
T cell immunotherapy is now a mainstay therapy for several blood-borne cancers as well as metastatic melanoma. Unfortunately, many epithelial tumors respond poorly to immunotherapy, and the reasons for this are not well understood. Cancer-associated fibroblasts (CAFs) are the most frequent non-neoplastic cell type in most solid tumors, and they are emerging as a key player in immunotherapy resistance. A range of immortalized CAF lines will be essential tools that will allow us to understand immune responses against cancer and develop novel strategies for cancer immunotherapy. To study the effect of CAFs on T cell proliferation, we created and characterized a number of novel immortalized human CAFs lines (Im-CAFs) from human breast, colon, and pancreatic carcinomas. Im-CAFs shared similar phenotypes, matrix remodeling and contraction capabilities, and growth and migration rates compared to the primary CAFs. Using primary isolates from breast carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma, we report that CAFs across major tumor types are able to potently suppress T cell proliferation in vitro. Im-CAFs retained this property. Im-CAFs are a key tool that will provide important insights into the mechanisms of CAF-mediated T cell suppression through techniques such as CRISPR-Cas9 modification, molecular screens, and pipeline drug testing. |
topic |
Stromal cells T cells cancer-associated fibroblasts tumor microenvironment tumor immunology |
url |
https://www.mdpi.com/1422-0067/22/4/1827 |
work_keys_str_mv |
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