Abstract
Cancer associated fibroblasts are a prominent component of the tumour microenvironment in most solid cancers. This heterogeneous population of cells are known to play an important role in tumour progression and recent studies have demonstrated that CAFs may confer resistance to checkpoint immunotherapy, suggesting that targeting these cells could improve response rates. However, effective clinical strategies for CAF targeting have yet to be identified. In this editorial, we highlight current limitations in our understanding of CAF heterogeneity, and discuss the potential and possible approaches for CAF-directed therapy.
Highlights
Immunotherapies are increasingly used as firstline treatments for solid cancers
We showed that NOX4 inhibition could reverse TGF-β1 mediated Cancer associated fibroblast (CAF) activation, leading to reduced extra-cellular matrix (ECM) deposition, increased CD8+ T-cell infiltration into tumours and improved immunotherapy efficacy
There is significant pre-clinical data to suggest that CAF targeting could increase immunotherapy efficacy
Summary
Immunotherapies are increasingly used as firstline treatments for solid cancers. only a subset of patients respond and the size of this subset varies significantly between tumour types. Cancer associated fibroblast (CAF) targeting is one strategy for enhancing immunotherapy efficacy in pre-clinical models and may improve patient response rates. In a recent study [1], we showed that CAFs prevent CD8+ T-cells from infiltrating solid tumours by inducing CTLA4 upregulation, which led to abrogated immunotherapy (anti-PD1 and anticancer vaccination) efficacy.
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