Abstract
Over the past decade, T cell immunotherapy has changed the face of cancer treatment, providing robust treatment options for several previously intractable cancers. Unfortunately, many epithelial tumors with high mortality rates respond poorly to immunotherapy, and an understanding of the key impediments is urgently required. Cancer-associated fibroblasts (CAFs) comprise the most frequent nonneoplastic cellular component in most solid tumors. Far from an inert scaffold, CAFs significantly influence tumor neogenesis, persistence, and metastasis and are emerging as a key player in immunotherapy resistance. In this review, we discuss the physical and chemical barriers that CAFs place between effector T cells and their tumor cell targets, and the therapies poised to target them.
Footnotes
This work was supported by a Monash Graduate Scholarship (to A.T.B.), a Monash Fellowship (to A.L.F.), the Saudi Arabian Cultural Mission, affiliate to the Royal Embassy of Saudi Arabia in Australia, and Ministry of Education, Saudi Arabia (to M.H.A.), Cabrini Foundation Research Grant ST081 (to S.W. and A.L.F.), and Let’s Beat Bowel Cancer (to S.W.). Funders played no role in manuscript preparation or content.
Abbreviations used in this article:
- CAF
- cancer-associated fibroblast
- CAR-T
- T cell with high-affinity chimeric Ag receptor
- CMS
- consensus molecular subtype
- ECM
- extracellular matrix
- FAP
- fibroblast activation protein
- myCAF
- myofibroblastic CAF
- NSCLC
- non–small cell lung cancer
- PDAC
- pancreatic ductal adenocarcinoma
- PD-L
- programmed death ligand
- PDPN
- podoplanin
- RNA-Seq
- RNA sequencing
- αSMA
- α smooth muscle actin
- TIL
- tumor-infiltrating lymphocyte
- TLT
- tertiary lymphoid tissue
- Treg
- regulatory T cell.
- Received October 23, 2020.
- Accepted November 6, 2020.
- Copyright © 2021 by The American Association of Immunologists, Inc.
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Log in using your username and password
In this issue
