Synapse - Ectopic activation of the miR-200c–EpCAM axis enhances antitumor T cell responses in models of adoptive cell therapy

Ectopic activation of the miR-200c–EpCAM axis enhances antitumor T cell responses in models of adoptive cell therapy Journal Article

Authors:	Zhang, M.; Zhao, Z.; Pritykin, Y.; Hannum, M.; Scott, A. C.; Kuo, F.; Sanghvi, V.; Chan, T. A.; Seshan, V.; Wendel, H. G.; Schietinger, A.; Sadelain, M.; Huse, M.
Article Title:	Ectopic activation of the miR-200c–EpCAM axis enhances antitumor T cell responses in models of adoptive cell therapy
Abstract:	Adoptive T cell therapy (ACT) is a promising strategy for treating cancer, but it often fails because of cell intrinsic regulatory programs that limit the degree or duration of T cell function. In this study, we found that ectopic expression of microRNA-200c (miR-200c) markedly enhanced the antitumor activity of CD8+ cytotoxic T lymphocytes (CTLs) during ACT in multiple mouse models. CTLs transduced with miR-200c exhibited reduced apoptosis during engraftment and enhanced in vivo persistence, accompanied by up-regulation of the transcriptional regulator T cell factor 1 (TCF1) and the inflammatory cytokine tumor necrosis factor (TNF). miR-200c elicited these changes by suppressing the transcription factor Zeb1 and thereby inducing genes characteristic of epithelial cells. Overexpression of one of these genes, Epcam, was sufficient to augment therapeutic T cell responses against both solid and liquid tumors. These results identify the miR-200c–EpCAM axis as an avenue for improving ACT and demonstrate that select genetic perturbations can produce phenotypically distinct T cells with advantageous therapeutic properties. Copyright © 2021 The Authors, some rights reserved;
Journal Title:	Science Translational Medicine
Volume:	13
Issue:	611
ISSN:	1946-6234
Publisher:	American Association for the Advancement of Science
Date Published:	2021-09-15
Start Page:	eabg4328
Language:	English
DOI:	10.1126/scitranslmed.abg4328
PROVIDER:	scopus
PUBMED:	34524864
PMCID:	PMC9374309
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85115180621&doi=10.1126%2fscitranslmed.abg4328&partnerID=40&md5=fd12243dc6cd550ea4ebe72fb3e65d16
Notes:	Article -- Export Date: 1 October 2021 -- Source: Scopus