miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment

Regina Lin; John H Sampson; Qi-Jing Li; Bo Zhu

doi:10.4161/2162402X.2014.990803

miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment

Oncoimmunology. 2015 Apr 2;4(3):e990803. doi: 10.4161/2162402X.2014.990803. eCollection 2015 Mar.

Authors

Regina Lin¹, John H Sampson², Qi-Jing Li¹, Bo Zhu³

Affiliations

¹ Department of Immunology; Duke University Medical Center ; Durham, NC, USA.
² Department of Immunology; Duke University Medical Center ; Durham, NC, USA ; Department of Neurosurgery; Duke University Medical Center ; Durham, NC, USA.
³ Institute of Cancer; Xinqiao Hospital ; The Third Military Medical University ; Chongqing, China.

Abstract

In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic CD8⁺ T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We have demonstrated that miR-23a blockade in tumor-specific CTLs conferred resilience to TGFβ-mediated immunosuppression, resulting in superior tumor control. Our studies highlight miR-23a in tumor-specific CTLs as a clinically relevant target to enhance ACT.

Keywords: TGFβ; cancer immunotherapy; cytotoxic CD8+ T lymphocytes; immune evasion; microRNA.