Table 1. Summary of the main CAF subsets and features in each organ.
| Organ | Organism | Central Features | Signature/Markers | Total Number of Analyzed Fibroblasts | Ref. | |
|---|---|---|---|---|---|---|
| Inflammatory | Breast | Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors) | Inflammation, immune trafficking, and complement | Ly6c1,Il-6,Il-33, Cxcl1,Cxcl12,Ccl2,Ccl7, C3,C4b, C1s1, C1s2 | 535 | 51 |
| Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors), human TNBC samples | Inflammation | PDPN, subdivided into 2 populations characterized by CXCL1 and IL-6 | 8,033 | 13 | ||
| MMTV-PyMT model, human BC tissue samples | Inflammation and chemotaxis | Cxcl14 | 768 | 30 | ||
| Human BC | Inflammatory response, TNF signaling, cytokine pathway | CXCL12, SOD2. Additional pathways: detoxification (ADH1B and GPX3), response to stimuli (RGMA and SCARA5) | 18,296 | 78 | ||
| PyMT/WT, PyMT/ELF5 | Inflammatory response, complement activation, monocyte recruitment | Involuting CAF signature-CXCL12, Ly6c1, C3, C4b | 2,255 | 80 | ||
| Human TNBC | Inflammation and chemotaxis | IGF1, FIGF, PDGFD,CXCL12 and CXCL13. As opposed to myCAFs, iCAFs characterized by FAPLOW/CD90LOW | 1,409 | 79 | ||
| Pancreas | Human IPMNs and PDAC tissue | Inflammation | VIM, FAP, COL3A1, DES, IL6, and CXCL12 | ≥ 267 | 48 | |
| KPP, PRT, KIC, KPC&KPfCmouse models of PDAC; Human PDAC | Chemoattraction, inflammation, immune trafficking, complement regulation | Cxcl1/2/9/10/12, Cxcl1, Ccl2/7, Il-6/8,IL-1R1,LIF,CFD, C7, C3, C1s,C1r, Pdgfra | 962 (human) & 4,012 (mice) [44]; 8,439 [46]; 5,802 [47]; 2,143 [49]; ~ 10,900 (mice)& 8,931 (human) [50]; 12,239 [71]; 1,753 [72] | 44,46,47,49,50,71,72 | ||
| Lung | Human NSCLC;Murine lung adenocarcinoma model (KrasLA1) | Inflammation, chemotaxis | CXCL12/14, PDGFRA | 3,794 [36];428 [83] | 36,83 | |
| Ovaries | Human ovarian cancer | Inflammation, complement regulation, and chemotaxis | IL-1/6/10, CXCL1/2/1012/14, CCL2, SOCS3,C3/7,C1QA/B/C,CFD,CFB,SERPING1 | 7,760 [56]; 547 [57] | 56,57 | |
| Liver | Human ICC;Murine ICC models (YAP/AKT, KRAS/p19) | Inflammation, chemotaxis, complement, HGF-met signaling | FBLN1, IGFI, CXCL1/12, IGFBP6, SLPI, SAA1, C3, C7, Il-6,HGF,CCL21 | 498 [54]; 12,431 (mice) & 4,463 (human) [88] | 54,89 | |
| Bladder | Human urothelial bladder carcinoma | Inflammation and chemotaxis | CXCL12, IL6, CXCL14, CXCL1, and CXCL2, marked by PDGFRA | N.A. | 58 | |
| Skin | Murine Melanoma | Immune trafficking and inflammation. | Marked by Pdpn, Pdgfra, and Cd34: Cxcl12, Csf1, and Ccl8, Il6ra and Il6st, C3, C2, and C4b | N.A. | 38 | |
| Immune Regulatory | Breast | Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors) | Antigen presentation, MHC-II genes | CD74, H2-Aa, H2-Ab1, H2-Eb, Cd74 | 535 | 51 |
| Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors), human TNBC samples | Immune regulation, chemotaxis | PDPN subpopulation subdivided into Ly6c+, CXCL12, Saa3 subsets | 8,033 | 13 | ||
| Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors), human TNBC samples | MHC-II presentation and immune regulation | S100A4, CD73,H2-Aa, H2-Ab1 and CD74; SLPI and SPP1 | 8,033 | 13 | ||
| Human BC | IFNγ, cytokine signaling, MHCII presentation | CCl19, CCl5, CD74 | 18,296 | 78 | ||
| Human TNBC | Immune regulation | CXCL12 hallmark gene, C5-C5AR1 signaling and TGFB1-TGFBR1 and TGFB2-TGFBR1 axis. CXCL12-CXCR4 and CXCL13-CXCR5 signaling. | 1,409 | 79 | ||
| Pancreas | Human PDAC | Immune regulation via Complement secretion | C3, C7, CFB, CFD, CFH, CFI | 2,958 | 73 | |
| KPP mice& human PDAC | Immuno-regulatory module | Pdgfc, Vegfa, Il33,Il18 | ~ 10,900 (mice)&8,931 (human) | 50 | ||
| Mouse (KPC model) &human PDACs | Antigen presentation, T-cell regulation | MHC-II in mice (H2-Aa and H2-Ab1, CD74) and human (HLA-DRA, HLA-DPA1,HLA-DQA, CD74). Additional immunoregulatory genes: BCAM, F11R, IRF5. | 962 (human) & 4,012 (mice) | 44 | ||
| PRT, KIC, KPC&KPfC mouse models of PDAC;Human PDAC | Antigen presentation, MHC-II genes | CD74, H2-Aa, H2-Dmb1,HLA-DQA1,CD83 | 2,143 [49];12,239 [71];1,753 [72] | 49,71,72 | ||
| Lung | Human lung adenocarcinoma | Immune modulation and antigen presentation | CFD,CXCL14,CXCL12, MHC-II,CD74 | 2,257 | 84 | |
| Prostate | Human prostate cancer | Inflammation, regulation of myeloid cell recruitment | CCL2,CXCL12,CCL11,CXCL1,IL33 | 3,321 | 86 | |
| Liver | Mouse model of liver metastasis (PDAC/CRC tumor cell lines injection)/human CRC liver metastases | Inflammation, IFN response, HGF-Met signaling, antigen expression | HG, H2-Q4, H2-Q7, Ifitm. | N.A. | 55 | |
| Murine ICC model, human ICC | Antigen presentation | CD74, HLADRA, HLA-DRB1, H2-Q4 | 498 [54]; 12,431 (mice) & 4,463 (human) [88] | 54,89 | ||
| Antigen Presentation | Pancreas | Mouse (KPC model) and human PDACs | Antigen presentation (AP); Partial activation of CD4+ T-cells (by TCR ligation) | Mouse: H2-Aa, H2-Ab1 and CD74; SAA3 and SLPI. Human: HLA-DRA, HLA-DPA1, HLA-DQA1, and CD74; SLPI | 962 (human) & 4,012 (mice) | 44 |
| Mouse model of human PDAC (cell line-derived xenograft; CDX) | AP | CD74 and HLA-DRA | 699 | 45 | ||
| Tamoxife-ninducible mouse model of PDAC (PRT) | AP | H2-Aa, CD74 and CD83 | 12,239 | 71 | ||
| KPP mouse model of PDAC | AP | H2-Ab1 and CD74; SAA3 | ~ 10,900 (mice) & 8,931 (human) | 50 | ||
| KIC, KPC&KPfC mouse models of PDAC | AP; Partial activation of CD4+ T-cells (by TCR ligation); Induction of NaïveCD4+ T-cells into regulatory T-cells | H2-Aa, H2-Ab1, H2-Eb1, and CD74; MSLN, UPK3b, LRRN4 and KRT19 (mesothelial genes) | 17,055 (Derived from integrated data of 3 papers: Hosein, Elyada&Domingues) | 11 | ||
| Breast | Mouse allograft model of TNBC (BALB/Cderived 4T1 mammary tumors) | AP | H2-Aa, H2-Ab1 and CD74; SLPI and SPP1 | 8,033 | 13 | |
| Liver | Human ICC | AP | HLA-DRA, HLA-DRB1 and CD74, | 498 | 54 | |
| Lung | Human & mouse (LLC model) lung tumors | AP; Formation of functional spots within tumors that sustain CD4+ T-cells; Priming CD4+ T-cells along with rescuing them from apoptosis | Human: CD74 and SLPI; IL-6, CFD, C1QA, and C1QB. Mouse: CD74 and SLPI | 798 (human), N.A. (mice) | 92 | |
| ECM-remodeling/ myofibroblastic CAFs | Pancreas | Mouse (KPC model) and human PDACs | Smooth muscle contraction, focal adhesion, ECM organization, and collagen formation | Mouse: ACTA2, TAGLN, IGFBP3, THY1,COL12A1 and THBS2 Human: ACTA2, TAGLN, MYL9, TPM1, TPM2, MMP11, POSTN and HOPX |
962 (human) &4,012 (mice) | 44 |
| Mouse model of human PDAC (cell line-derived xenograft; CDX) | ECM organization, cell adhesion, and blood vessel development | ACTA2, TAGLN, BGN, COL8A1, COL15A1, IGFBP7, TPM1 and TPM2 | 699 | 45 | ||
| Human PDAC | Focal adhesion and ECM-receptor interactions | COL10A1 and POSTN | 8,439 | 46 | ||
| Human PDAC | ECM remodeling | ACTA2, MYL9, and POSTN | 5,802 | 47 | ||
| Human IPMNs and PDAC tissue | ECM remodeling | ACTA2 | ≥ 267 | 48 | ||
| Breast | Mouse allograft model of TNBC (BALB/C-derived 4T1 mammary tumors) | ECM organization and wound healing features | ACTA2, THBS2, FBN1, and MFAP5 | 8,033 | 13 | |
| 535 | 51 | |||||
| Transgenic mouse model of breast cancer (MMTV-PyMT) | ECM molecules production | DCN, LUM, VCAN, COL14A1, FBLN1, FBLN2, SMOC, LOX, LOXL1, PDGFRα, and CXCL14 | 768 | 30 | ||
| Lungs | Human NSCLC | Myogenesis, NOTCH pathway, and angiogenesis | ACTA2, MEF2C, MYH11, ITGA7, COL4A1, and COL10A1 | 1,465 | 37 | |
| Human NSCLC | ECM remodeling | COL13A1, COL14A1, ACTA2,TAGLN, MYH11, MYLK, and ACTG2 | 3,794 | 36 | ||
| Liver | Human ICC | ECM and collagen fibril organization | POSTN, FN1, LUM, DCN, VCAN, COL5A1, COL5A2, and COL63A | 498 | 54 | |
| Mouse model of liver metastasis (PDAC/CRC tumor cell lines injection)/human CRC liver metastases | ECM remolding/Opposing effects on tumor growth | Mouse: ACTA2, COL1A1, and COL3A1. Human: COL1A1, COL3A1, and COL63A | N.A. | 55 | ||
| Ovary | Human ovarian cancer | TGβ-induced reactive stroma | ACTA2, POSTN, COMP, COL10A1, COL11A1, MMP11, TAGLN, and FN1 | 7,760 | 56 | |
| Skin | Melanoma mouse model | Desmoplastic reaction/Contraction of actin stress fibers | PDPN, PDGFRα, POSTN, and TNC/ACTA2, ROCK1, MLC2, and MLCK | N.A. | 38 | |
| Bone | Human osteosarcoma | ECM remodeling | COL14A1/ ACTA2, MYL9, and LUM | N.A. | 40 | |
| Colon | Human CRC | Cytoskeleton/ECM remodeling | ACTA2, TAGLN, and PDGFA/ MMP2, DCN, and COL1A2 | 26 | 41 | |
| Urinary bladder | Human urothelial bladder carcinoma | Focal adhesion and contraction | RGS5, MYL9, and MYH11 | N.A. | 58 |