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Article

In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts

1
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
3
Australian Regenerative Medicine Institute, Monash University, Clayton 3800, Australia
4
Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston B15 2TT, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Stephanie Gras
Int. J. Mol. Sci. 2021, 22(4), 1827; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041827
Received: 5 November 2020 / Revised: 3 February 2021 / Accepted: 4 February 2021 / Published: 12 February 2021
(This article belongs to the Special Issue Recent Advances in T Cell Immunity)
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. View Full-Text
Keywords: Stromal cells; T cells; cancer-associated fibroblasts; tumor microenvironment; tumor immunology Stromal cells; T cells; cancer-associated fibroblasts; tumor microenvironment; tumor immunology
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MDPI and ACS Style

Abuwarwar, M.H.; Baker, A.T.; Harding, J.; Payne, N.L.; Nagy, A.; Knoblich, K.; Fletcher, A.L. In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts. Int. J. Mol. Sci. 2021, 22, 1827. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041827

AMA Style

Abuwarwar MH, Baker AT, Harding J, Payne NL, Nagy A, Knoblich K, Fletcher AL. In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts. International Journal of Molecular Sciences. 2021; 22(4):1827. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041827

Chicago/Turabian Style

Abuwarwar, Mohammed H., Alfie T. Baker, Jeffrey Harding, Natalie L. Payne, Andras Nagy, Konstantin Knoblich, and Anne L. Fletcher 2021. "In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts" International Journal of Molecular Sciences 22, no. 4: 1827. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041827

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