Table 1:

Characteristic features of the unique cancer-associated fibroblasts subtypes.

CAF subtype	CAF subtype markers	CAF subtype functions	References
LRRC15+ CAF	LRRC15	Poor response to anti-PD-L1 cancer immunotherapy increases with tumor progression	Dominguez et al.149
PDPN+ CAFs	PDPN	Worse prognosis	Hu et al. 150, Friedman et al.151
FAP+ CAF	FAP	Block CD8+ antitumor T cells	Zhang et al.152, Feig et al.153, Grout et al. 154
Steady state-like CAF	PI16, DPP4	Similar to NF	Foster et al.155
Mechanorespo nsive CAF	αSMA, POSTN, FSP1, PDGFRα	Express mechanosensitive signaling mediators and ECM components	Foster et al.155
Immunomodul atory CAF	Il1r1, Myd88, Il6st, Cxcl1	Modulates inflammatory TME	Foster et al.155
CD10+GPR77 + CAF	CD10, GPR77	Sustain cancer stemness, promote cancer formation and chemoresistance	Su et al. 156
ECM CAF	MMP14, LOXL2, POSTN	ECM remodeling, fatty acid metabolism, peroxisome, invasion, shorter overall survival	Li et al.157, Valdés-Mora et al.158
PDGFRα+ SAA1+ CAF	PDGFRα, SAA1	Stimulate tumor growth in mice	Djurec et al.159
Cancer-restraining CAF	Meflin	Favorable patient outcome, tumor vessel perfusion, regulate collagen structure	Mizutani et al.160
Activated metabolic state CAF	PLA2G2A, CRABP2	Highly active glycolysis, increased metastasis, and poor prognosis, found in patients with low desmoplasia	Wang et al.161
Igfbp5+ CAF	IGFBP5, FN1, LY6C1	Found in early PanIN lesions	Schlesinger et al.162
Complement-secreting CAF	C3, C7, CFD	Complement system, regulates immune and inflammation response	Chen et al.163
Classical CAF	COL1A1, FAP	ECM deposition	Chen et al.163
FAP+ αSMA+ CAF	αSMA, FAP	Dense ECM deposition, decreases T-cell infiltration, present in early-stage tumors	Grout et al.154
MYH11+ αSMA+ CAF	αSMA, MYH11	Dense ECM deposition, which decreases T-cell infiltration, appears in more advanced tumors	Grout et al.154
S100A4+ CAF	FSP1	ECM remodeling, antigen presentation	Friedman et al.151
CD53high CAF	CD53	Small proportion of CAFs, cytoplasmic intermediate filament, matrix glycoproteins, integrins, MMP inhibitors	Sebastian et al.164
Crabp1high CAF	CRABP1	Small proportion of CAFs, ECM proteins, collagens, laminins, MMPs	Sebastian et al.164
Mesothelial CAF	UPK1B, MSLN, KRT19	Portal fibroblast and mesothelial markers	Affo et al.165
Portal CAF	PRELP, PDGFRα, MMP23B	Minority CAF population, widely interacts with other TME cells, decreases angiogenesis, tumor restraining function	Chiavarina et al. 166
Vascular smooth muscle CAF	CNN1, MYH11	Unknown	Chiavarina et al. 166
Entoderm-related CAF	COL1A1, POSTN, CTHRC1	Secrete growth factors, negatively associated with the abundance of M1 macrophages	Zhao et al.167
Adhesion-related CAF	RGS5, NDUFA4L2, ADIRF	Adherens junctions, decreases patient survival	Zhao et al.167
Vascular-related CAF	IGLC7, SPINK4, TFF1	Vasculature development	Zhao et al.167
Mesenchyme-related CAF	CXCL14, TMEM176B, F3	Immune checkpoint interactions with other CAF subtypes	Zhao et al.167
Endoplasmic reticulum-related CAF	SERPINE1, IGF1, S100A10	IL-6 signaling, negatively associated with the abundance of M2 macrophages	Zhao et al.167
Cell cycle-related CAF	HIST1H4C, TK1, BIRC5	Increases patient survival, interacts with other CAF subtypes via the TIMP1-CD63 signaling pathway	Zhao et al.167
Divergent CAF	PAX3, NRP2, EDNRB	Mesenchymal/neural crest development and amoeboidal cell movement	Costea et al.168
Interferon-regulated CAF	SLC14A1	Induced by IFN signaling, confers stemness to cancer cells via the WNT5A paracrine pathway, unfavorable clinical outcomes	Ma et al.169
STAR+ CAF	STAR, TSPAN8, ALDH1A1	Enriched after chemotherapy	Loret et al.170