Available online 17 June 2022, 108231
AbstractCancer-associated fibroblasts (CAFs) are a common cell in the tumour microenvironment with diverse tumour-promoting functions. Their presence in tumours is commonly associated with poor prognosis making them attractive therapeutic targets, particularly in the context of immunotherapy where CAFs have been shown to promote resistance to checkpoint blockade. Previous attempts to inhibit CAFs clinically have not been successful, however, in part due to a lack of understanding of CAF heterogeneity and function, with some fibroblast populations potentially being tumour suppressive. Recent single-cell transcriptomic studies have advanced our understanding of fibroblast phenotypes in normal tissues and cancers, allowing for a more precise characterisation of CAF subsets and providing opportunities to develop new therapies. Here we review recent advances in the field, focusing on the evolving area of therapeutic CAF targeting.
KeywordsTumour microenvironment
Fibroblast
Myofibroblast
Cancer-associated fibroblast
Stromal targeting
Immunotherapy
Abbreviations⍺SMAalpha Smooth Muscle Actin
apCAFAntigen Presenting CAF
ATRAAll-trans Retinoic Acid
CAFCancer-Associated Fibroblast
CAR-TChimeric Antigen Receptor Expressing T cell
CCLC-C Motif Chemokine Ligand
CTLA-4Cytotoxic T-Lymphocyte Associated Protein 4
CXCLC-X-C Motif Chemokine Ligand
CXCRC-X-C Motif Chemokine Receptor
EMTEpithelial-Mesenchymal Transition
FAPFibroblast Activation Protein
LIFLeukaemia Inhibitory Factor
LPARLysophosphatidic Acid Receptor
MDSCMyeloid Derived Suppressor Cell
MHCMajor Histocompatibility Complex
myoCAFMyofibroblastic CAF
PD-1Programmed Cell Death Protein 1
PDACPancreatic Ductal Adenocarcinoma
PDGFPlatelet Derived Growth Factor
PD-L1Programmed Death Ligand 1
PSCPancreatic Stellate Cell
ROSReactive Oxygen Species
scRNA-SeqSingle-cell RNA Sequencing
SMADSuppressor of Mothers against Decapentaplegic
STATSignal Transducer and Activator of Transcription
TGF-β1Transforming Growth Factor beta 1
TMETumour Microenvironment
TNF-⍺Tumour Necrosis Factor alpha
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