Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Mao, Xiaoqi; Xu, Jin; Wang, Wei; Liang, Chen; Hua, Jie; Liu, Jiang; Zhang, Bo; Meng, Qingcai; Yu, Xianjun; Shi, Si

doi:10.1186/s12943-021-01428-1

Molecular Cancer

Table 2 Phenotypic and functional heterogeneity of cancer-associated fibroblasts exhibited in distinct tumor types

From: Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Cancer types	Subtypes	Characteristic markers/ expression/secretion	Functions	Refs
PDAC	myCAFs (pCAFs)	α-SMA, TAGLN, MYL9, TPM1, TPM2, POSTN and MMP11	Tumor proliferation, Migration, Invasion and ECM remodeling	[92, 93, 103]
	iCAFs (pCAFs)	PDGFRα, HAS1, HAS2, IL-6, IL-8, IL-11, CXCL1, CXCL2 and CCL2	Immune suppression, Cachexia and Chemoresistance	[92, 93, 103]
	apCAFs (pCAFs)	MHC class II, H2-Aa, H2-Ab1 and CD74	Antigen-present, Immune modulation	[93, 94, 103]
PDAC	CAF-A	POSTN	Tumor proliferation, Invasion, Metastasis	[95]
	CAF-B	MYH11	Lymph-node metastasis, Prognostic factor (adverse)	[95]
	CAF-C	PDPN	Immune promotion, Prognostic factor (favorable)	[95]
Breast cancer	CAF-S1	CD29, FAP, α-SMA, PDGFRβ, FSP1 and CXCL12	Tumor proliferation, Migration, Lymph-nodes metastasis, Immune suppression and EMT initiation	[96, 98]
	CAF-S2	Not reported	Not reported	[96, 98]
	CAF-S3	CD29, FSP1, PDGFRβ	Not reported	[96, 98]
	CAF-S4	CD29, FSP1, PDGFRβ and α-SMA	Tumor invasion, Migration, Lymph-nodes metastasis	[96, 98]
Breast cancer	myCAFs	α-SMA, ACTA2, TAGLN, MYL9, IGFBP-3 and TNC	Tumor proliferation, Migration, Invasion, Angiogenesis and EMT	[99]
	iCAFs	Ly6c1, CLEC3B, HAS1, DPT and COL14A1	Tumor proliferation, Metastasis, Angiogenesis, Immune evasion and Chemoresistance	[99]
	apCAFs	CD74, H2-Aa, H2-Ab1, H2-Eb1, KRT18 and FSP1	Antigen-present, Immune modulation	[99]
Breast cancer	vCAFs/cCAF (proliferative segment of vCAFs)	Notch3, EPAS1, COL18A1 and NR2F2 (perivascular cells)	Angiogenesis	[100]
	mCAFs	Fibulin-1, PDGFRα and CXCL14 (resident fibroblasts)	Immune regulation	[100]
	dCAFs	SCRG1 (malignant cells)	Not reported	[100]
Breast cancer	CD10⁺GPR77⁺	CD10 and GPR77	Chemoresistance	[104]
OSCC	CAF-N	HA, MMPs	Tumor invasion, Immunosuppression	[101]
OSCC	CAF-D	TGF-β	Tumor migration	[101]
Colorectal cancer	CAF-A	MMP2, DCN, αFAP and COL1A2	ECM remodeling	[102]
Colorectal cancer	CAF-B	α-SMA, ACTA2, TAGLN and PDGFA	Not reported	[102]
HGSOC	CAF-S1	CD29, FAP, αSMA, FSP1, PDGFRβ and CXCL12β	Tumor proliferation, Immune suppression	[97]
	CAF-S2 (non-activated)	Not reported	Not reported	[97]
	CAF-S3 (non-activated)	CD29, FSP1 and PDGFRβ	Not reported	[97]
	CAF-S4	CD29, αSMA, FSP1 and PDGFRβ	Tumor proliferation	[97]
PDAC/Oral/Colon/Bladder/Intestinal cancers	rCAFs	Meflin, BMP-4, Hedgehog and IKKβ	Antitumoral effect	[10, 105,106,107,108,109,110,111]

Multiple phenotype and function heterogeneous cancer-associated fibroblast subsets in distinct tumor types
PDAC pancreatic ductal adenocarcinoma, myCAFs myofibroblastic cancer-associated fibroblasts, iCAFs inflammatory cancer-associated fibroblasts, apCAFs antigen-presenting cancer-associated fibroblasts, pCAFs cancer-promoting cancer-associated fibroblasts, α-SMA alpha smooth muscle actin, TAGLN transgelin, MYL9 myosin light chain 9, TPM1 tropomyosin 1, TPM2 tropomyosin 2, POSTN periostin, MMP11 matrix metalloproteinase 11, PDGFRα platelet-derived growth factor receptor alpha, HAS1 hyaluronan synthase 1, HAS2 hyaluronan synthase 2, IL-6 interleukin-6, IL-8 interleukin-8, IL-11 interleukin-11, CXCL1 C-X-C chemokine ligand 1, CXCL2 C-X-C chemokine ligand 2, CCL2 C–C chemokine ligand 2, MHC class II major histocompatibility complex class II, H2-Aa histocompatibility 2 class II antigen A alpha, H2-Ab1 histocompatibility 2, class II antigen A, beta 1, CD74 cluster of differentiation 74, ECM extracellular matrix, MYH11 myosin-11, PDPN podoplanin, CD29 cluster of differentiation 29, FAP fibroblast activation protein, PDGFRβ platelet-derived growth factor receptor β, FSP1 fibroblast-specific protein 1, CXCL12 C-X-C chemokine ligand 12, EMT epithelial-mesenchymal transition, ACTA2 actin alpha 2, IGFBP-3 IGF-binding protein 3, TNC Tenascin-C, Ly6c1 lymphocyte antigen 6 complex, locus C1, CLEC3B C-type lectin domain family 3, member B, DPT dermatopontin, COL14A1 collagen type XIV alpha 1, H2-Eb1 histocompatibility 2, class II antigen E, beta 1, KRT18 keratin 18, EPAS1 endothelial PAS domain protein 1, COL18A1 collagen, type XVIII, alpha 1, NR2F2 nuclear receptor subfamily 2 group F member 2, CXCL14 C-X-C chemokine ligand 14, SCRG1 scrapie responsive gene 1, CD10 cluster of differentiation 10, GPR77 G protein-coupled receptor 77, OSCC oral squamous cell carcinoma, HA hyaluronan, TGF-β transforming growth factor beta, MMP2 matrix metalloproteinase 2, DCN decorin, COL1A2 collagen type 1 Alpha 2, PDGFA platelet derived growth factor A, HGSOC high-grade serous ovarian cancer, rCAFs cancer-restraining cancer-associated fibroblasts, BMP-4 bone morphogenetic protein 4, IKKβ inhibitor kappa B kinase beta

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