Table 1.
Cancer-associated fibroblast subtypes found in tumor tissues as revealed by single cell RNA sequencing.
| Cancer type/models | CAF subtypes | Markers/gene signature | Significance | References |
|---|---|---|---|---|
| Lung adenocarcinoma | Matrix fibroblasts | COL13A1+, COL14A1+ | Present majorly in early-stage tumor tissues | (30, 31) |
| Fibroblastic reticular cells | PDPN, PDGFRA | Immunologically specialized myofibroblasts that gather immune cells into the lymph node, support T cell, and B cell survival but prevent their activation, maintains dendritic cell migration | ||
| PDAC (Human+Mouse) | Myofibroblasts | α-SMA++, TAGLN, MYL9, TPM1, TPM2, MMP11, POSTN, HOPX (contractile proteins) | Found primarily adjacent to the cancer cells, Smooth muscle contraction, focal adhesion, ECM organization, collagen formation | (32) |
| Inflammatory CAFs (iCAFs) |
CLEC3B, PDGFRα, CFD, LMNA, DPT, AGTR1, HAS1, HAS2 (matrix proteins) IL6, IL8, chemokines CXCL1, CXCL2, CCL2, and CXCL12 |
Found in desmoplastic areas away from tumors, activate inflammatory pathways such as IFNγ response, TNF/NF-κB, IL2/STAT5, IL6/JAK/STAT3, and the complement pathway | ||
| PDAC (Human) | Antigen-presenting CAFs (apCAFs) | COL1A1, COL1A2, DCN, PDPN, MHCII genes (HLA-DRA, HLA-DPA1, and HLA-DQA), CD74 | Have immunomodulatory capacity (activate CD4+ T cells), involved in antigen presentation and processing, fatty-acid metabolism, MYC targets, and MTORC1 signaling | (28, 29) |
| Lipofibroblasts | FABP4, CAR3 | Lipid droplet–containing fibroblasts, express lipid metabolism genes | ||
| Breast Cancer | CAF-S1 | CD29+ FAP++ FSP1+ αSMA++PDGFRβ+ CAV1low | Key player in immunosuppression, promote differentiation of CD4+CD25+ T lymphocytes into CD25+FOXP3+ cells, characterized by cell adhesion, ECM organization, and immune response | (33) |
| CAF-S2 | CD29low FAP- FSP1 − /lowαSMA- PDGFRβ- CAV1 − | Mainly present in LumA tumors | ||
| CAF-S3 | CD29+ FAP- FSP1++αSMA-/low PDGFRβ+ CAV1-/low | Detected mainly in juxta-tumors | ||
| CAF-S4 | CD29++ FAP- FSP1+ αSMA++ PDGFRβ+ CAV1low | Activated CAF subset, detected in all tumor types LumA, TNBC, HER2, characterized by muscle contraction, regulation of actin cytoskeleton, and oxidative metabolism | ||
| Breast Cancer (MMTV-PyMTmouse model) |
Vascular CAFs (vCAFs) | vascular regulatory genes (NOTCH3, EPAS1, COL18A1, NR2F2), desmin, Nidogen-2 | Originated from perivascular location, significant role in vascular development and angiogenesis | (27) |
| Matrix CAFs (mCAFs) | ECM-related genes (DCN, LUM, AND VCAN), structural proteins (COL14A1), matricellular proteins (FBLN1, FBLN2,SMOC), and matrix-modifying enzymes (LOX, LOXL1), CXCL14 | Found mainly in normal tissues or early tumors, Resident fibroblasts, involved in ECM production, regulates tumor immune response | ||
| Cycling CAFs (cCAFs) | Similar to vCAFs but have differentially expressed cell cycle genes | Majority cells were in G2, M or S phase of cell cycle unlike others which are in G1 phase | ||
| Developmental CAFs (dCAFs) | stem cell genes (SCRG1, SOX9, AND SOX10), | Originated from malignant cells undergone EMT, involved in differentiation, development, and morphogenesis | ||
| Breast and lung cancer | CD10+GPR77+ CAFs | CD10, GPR77 | Chemoresistance, poor survival | (34) |
| PDAC | LRRC15+ CAFs | leucine-rich repeat-containing 15 (LRRC15), PDPN | TGF-β driven cell population, high expression is associated with poor anti-PD-L1 therapy response | (28) |