Targeting the epigenome to reinvigorate T cells for cancer immunotherapy

Table 1 circRNAs associated with CD8⁺ T cell exhaustion and immunosuppression

Cancer type	circRNA	Mechanism	References
NSCLC	circIGF2BP3^a, circHMGB2	Increases PKP3 expression via miR-328-3p and miR-3173-5p sponging, upregulating PD-L1 in tumor cells and inactivating the type I interferon response by inhibition of PRMT4 via miR-181a-5p sponging	[81]
	circRNA-002178^a	Upregulates PD-L1 expression in tumor cells and PD-1 expression in T cells respectively via miR-34a and miR-28-5p sponging	[84]
	circIGF2BP3^b	Increases PKP3 expression via miR-328-3p and miR-3173-5p sponging, upregulating PD-L1 in tumor cells	[85]
NPC	circBART2.2	Promotes transcription of PD-L1 through binding to the helicase domain of RIG-I, thereby activating transcription factors IRF3 and NF-κB	[86]
PC	circ_0046523	Upregulates PD-L1 expression in PC cells via miR-148a-3p sponging	[87]
HCC	circMET	Upregulates CXCL10 level through miR-30-5p sponging to abrogate Snail/DPP4-mediated immunosuppression	[88]
Melanoma	circ_0020710	Upregulates CXCL12 level via miR-370-3p sponging	[82]
BCa	circTRPS1^b	Upregulates PD-1 expression through enhancing GLS1-mediated glutamine metabolism via miR-141-3p sponging	[83]

^aAvailable as exosome-derived circRNAs; ^bFurther regulated by m⁶A modification; NSCLC non-small-cell lung cancer, NPC nasopharyngeal carcinoma, PC pancreatic cancer, BCa bladder cancer, PKP3 plakophilin 3, RIG iretinoic acid-inducible gene I, IRF3 interferon regulatory factor 3, NF-κB nuclear factor kappa-B, CXCL10 C-X-C motif chemokine ligand 10, GLS1 glutaminase 1, HCC hepatocellular carcinoma, PD-L1 programmed death-ligand 1, PRMT4 protein arginine methyltransferases 4

ISSN: 2054-9369