Overcoming stromal barriers to immuno-oncological responses via fibroblast activation protein-targeted therapy

W. Nathaniel Brennen, Daniel L. J Thorek, Wen Jiang, Timothy E. Krueger, Lizamma Antony, Samuel R. Denmeade, John T. Isaacs

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)155-175
Number of pages21
JournalImmunotherapy
Volume13
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • FAP
  • fibroblast activation protein
  • immunotherapy
  • prostate cancer
  • stroma
  • TGF-β
  • wound healing

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