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Cancer Lett. 2019 Apr 28;448:31-39. doi: 10.1016/j.canlet.2019.01.032. Epub 2019 Feb 5.

Drug delivery systems targeting tumor-associated fibroblasts for cancer immunotherapy.

Author information

1
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27559, USA; Department of Pharmaceutics, Collage of Pharmacy, Shandong University, Jinan, 250012, PR China.
2
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
3
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27559, USA. Electronic address: leafh@email.unc.edu.

Abstract

Solid tumors especially desmoplastic tumors are complex organ-like structures. Tumor-associated fibroblasts (TAFs), one type of the stromal cells, support the initiation, progression, and metastasis of carcinomas. TAFs also contribute to immunosuppressive tumor microenvironment (TME) and hinder T lymphocytes in killing tumors. Here, the role of TAFs in TME is discussed. In specific, TAFs form barriers for the penetration of T lymphocytes. TAFs also act as negative regulators for T lymphocytes. These findings suggest that targeting TAFs is a promising strategy for improving cancer immunotherapy. Our previous studies have indicated the ability of therapeutic nanoparticles to distribute into, and deplete or inactivate TAFs. This approach is discussed in the context of developing specific and effective immunotherapies for cancer.

KEYWORDS:

Cancer immunotherapy; Desmoplastic tumor; Drug delivery; Nanomedicine; Tumor microenvironment; Tumor-associated fibroblasts

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