Overcoming stromal barriers to immuno-oncological responses via fibroblast activation protein-targeted therapy.
W Nathaniel BrennenDaniel L J ThorekWen JiangTimothy E G KruegerLizamma AntonySamuel R DenmeadeJohn T IsaacsPublished in: Immunotherapy (2020)
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.
Keyphrases
- prostate cancer
- induced apoptosis
- radical prostatectomy
- cell cycle arrest
- bone marrow
- binding protein
- rectal cancer
- primary care
- poor prognosis
- signaling pathway
- protein protein
- endoplasmic reticulum stress
- endothelial cells
- electronic health record
- oxidative stress
- transforming growth factor
- cancer therapy
- robot assisted
- transcription factor
- drug delivery
- small molecule
- amino acid
- vascular endothelial growth factor
- epithelial mesenchymal transition
- cell proliferation
- squamous cell
- long non coding rna
- artificial intelligence