Overcoming stromal barriers to immuno-oncological responses via fibroblast activation protein-targeted therapy
Abstract
The tumor microenvironment contributes to disease progression through multiple mechanisms, including immune suppression mediated in part by fibroblast activation protein (FAP)-expressing cells. Herein, a review of FAP biology is presented, supplemented with primary data. This includes FAP expression in prostate cancer and activation of latent reservoirs of TGF-β and VEGF to produce a positive feedback loop. This collectively suggests a normal wound repair process subverted during cancer pathophysiology. There has been immense interest in targeting FAP for diagnostic, monitoring and therapeutic purposes. Until recently, this development has outpaced an understanding of the biology; impeding optimal translation into the clinic. A summary of these applications is provided with an emphasis on eliminating tumor-infiltrating FAP-positive cells to overcome stromal barriers to immuno-oncological responses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2021
- Source ID
- 10.2217/imt-2020-0066
Entities
People
- Daniel L J Thorek
- John T Isaacs
- Lizamma Antony
- Samuel Denmeade
- Timothy E Krueger
- W Nathaniel Brennen
- Wen Jiang
Organizations
- AbbVie
- Istituto Superiore di Sanità
- Johns Hopkins University
- United States Department of Defense
- Washington University in St. Louis