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 1 Various stimulating factors and their related activating mechanisms during cancer-associated fibroblast progression

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

Stimulating factors	Types	Activating mechanisms	Biology effects	Cancer models	Refs
TGF-β1	Growth factor	TGF-β1-SMAD signaling pathway	Induces tumor cell proinvasive properties	Colon cancer, Breast cancer	[35, 38]
SDF-1 (CXCL12)	Chemokine	SDF-1-CXCR4 autocrine signaling pathway	Maintains myofibroblast activation	Breast cancer	[38]
IL-1β	Proinflammatory cytokine	NF-κB signaling pathway	Enhances tumor-promoting inflammatory response	Squamous skin carcinoma	[29]
IL-6	Proinflammatory cytokine	JAK-ROCK-STAT3 signaling pathway	Facilitates CAF-induced ECM remodeling	Melanoma	[73]
DAMPs	Cell-necrosis-associated product	NLRP3 inflammasome signaling pathway	Promotes tumor growth and metastasis	Breast cancer	[74]
CD44v6/C1QBP complex	PDAC-derived exosomes	IGF-1 signaling pathway	Induces HSC activation, ECM remodeling and liver metastasis	PDAC	[45]
HSF-1	Transcription factor	Wnt and YAP/TAZ signaling pathway	Facilitates CAF aggressive behaviors (mediating ECM remodeling, cancer cell growth and invasion)	Breast, colorectal and ovarian cancer	[76]
LIF	Multifunctional cytokine	Epigenetic switch	Initiates and maintains CAF proinvasive phenotypes, promotes tumor invasion and ECM remodeling	Head and neck, lung and breast cancer	[77, 78]
ROS	Oxidative stress molecule	Autophagy and caveolin-1 dependent pathway	Promotes tumor migration, invasion and ECM remodeling	Breast cancer	[40, 79]
Matrix stiffening	Environmental stressor	SFK-YAP signaling pathway	Establishes a feed-forward self-reinforcing loop to maintain CAF phenotypes and enhance matrix remodeling	Breast cancer	[81]

Various stimulating factors of cancer-associated fibroblast activation and related activating mechanisms during their progression
TGF-β1 transforming growth factor-beta 1, SMAD Drosophila mothers against decapentaplegic protein, SDF-1 stromal-derived factor-1, CXCL12 C-X-C chemokine ligand 12, CXCR4 C-X-C chemokine receptor 4, IL-1β interleukin-1 beta, NF-κB nuclear factor-kappaB, IL-6 interleukin-6, JAK Janus kinase, ROCK Rho-associated kinase, STAT3 signal transducer and activator of transcription 3, CAF cancer-associated fibroblast, ECM extracellular matrix, DAMPs damage-associated molecular patterns, NLRP3 NOD-like receptor protein 3, PDAC pancreatic ductal adenocarcinoma, IGF-1 insulin-like growth factor-1, HSC hepatic stellate cell, HSF-1 heat shock factor-1, Wnt Wingless/dint-1 protein, YAP yes-associated protein, TAZ Tafazzin, LIF leukemia inhibitory factor, ROS reactive oxygen species, SFK SRC-family protein tyrosine kinase

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