Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy

Table 2 Immunotherapeutic strategies that target CAFs in clinical and/or preclinical studies

Drugs	Mechanisms	Combination therapy	Biological effects	Cancer models	Status	Refs
SynCon DNA vaccine	FAP deletion	Anti-tumor vaccine	Overcomes immune tolerance	Lung cancer	Preclinical	[100]
FAP-specific CAR T cell	FAP deletion	Anti-tumor CAR T cell	Enhances anti-tumor immunity	Lung cancer	Preclinical	[116]
Oncolytic adenovirus	FAP deletion	No	Enhances anti-tumor immunity	CRC	Preclinical	[118, 119]
ATAR (vitamin A analog)	Vitamin A storage and PSC deactivation	Gemcitabine	Enhances anti-tumor immunity; inhibits tumor cell growth	PDAC	Preclinical	[126]
Calcipotriol (vitamin D analog)	Vitamin D receptor activation and PSC deactivation	Anti-PD-1 immunotherapy	Reverses tumor immunosuppression	PDAC	Phase II	[10]
AMD3100	Blocks the CXCL12-CXCR4 interaction	Anti-PD-L1 immunotherapy	Reverses tumor immunosuppression	PDAC	Preclinical	[96]
¹³¹I-m81C6 (anti-tenascin mAb)	Radioimmunotherapy	No	Reverses tumor immunosuppression	Recurrent malignant glioma	Phase II	[135]
Ruxolitinib (JAK inhibitor)	JAK-STA3 pathway inhibition	Capecitabine	Inhibits tumor-promoting inflammation	Metastatic pancreatic cancer	Phase II	[129]
IPI-926	Hedgehog pathway inhibition	Gemcitabine	Reverses tumor immunosuppression	PDAC	Preclinical	[133]
NIS793 ABBV151	Blocking pan-TGF-β and GARP	Anti-PD-1 immunotherapy	Reverses tumor immunosuppression	Breast, lung, HCC, CRC, pancreatic and renal cancer	Phase I	[62]

FAP fibroblast activation protein, CAR chimeric antigen receptor, ATRA all-trans retinoic acid, CXCL12 CXC-chemokine ligand 12, CXCR4 CXC-chemokine receptor 4, PD-1 programmed cell death-1, PD-L1 programmed cell death 1 ligand, JAK Janus kinase, STAT3 signal transducer and activator of transcription 3, mAb monoclonal antibody, PSC pancreatic stellate cell, TGF-β transforming growth factor-β, GARP glycoprotein A repetitions predominant protein, PDAC pancreatic ductal adenocarcinoma, HCC hepatocellular carcinoma, CRC colorectal cancer

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