Drug delivery systems targeting tumor-associated fibroblasts for cancer immunotherapy

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.