Table 2.

Various siRNA and circRNAand Their Role in Cancer Immunotherapy

siRNA	Cancer type	In vitro/in vivo		Model		Function			references
ODC‐targeting siRNA	ESCC	in vitro		M2 macrophage		↓IL‐10 and TGF‐β, ↑IL‐12p35			[112]
STAT3+PD-L1 siRNA	Skin melanoma Breast cancer	in vitro		B16-F10 & 4T1 cell lines		↓PD-L1 and STAT3 genes Suppresses proliferation, migration, and angiogenesis suppresses cancer progression			[113]
		in vivo		BALB/C and C57BL/6J mice
siRNA-loaded nanocarrier	-	in vitro		CD8+ T-cells from human blood		enhanced T-cell survival ↓PD-L1			[114]
siRNA-loaded PCAnp	Colon cancer	in vitro		T cells of colon cancer bearing mice		enhanced T cell responses blockade of A2AR & CTLA-4			[115]
siRNA-PD-L1 imatinib in a liposomal NP	Melanoma	in vitro		B16F10 cells		↑cancer cell apoptosis delayed tumor growth			[116]
NP-siCD47 /CCL25	Breast Cancer	in vitro		4T1 cells		tumor infiltration of CCR9+CD8+ T cells ↓CD47,PD-1/PD-L1 blockade			[117]
IL-6- & STAT3 SiRNA+TMC Np	Breast Cancer Colorectal Cancer Melanoma	in vitro		4T1, CT26, B16-F10		↓IL-6/STAT3 expression			[118]
PD-1 siRNA/ PD-L1 siRNA loaded PLGA np	Colon cancer	in vitro		CTLs MC38 tumor-bearing mice		↓mTOR signaling cosilencing of PD-1 and PD-L1			[119]
		in vivo				showed more significant tumor growth suppression and long-term tumor inhibition in colon cancer
siRNA-PD-L1	-	in vitro		-		co-delivery of siRNA-PD-L1 and doxorubicin can block the inhibitory signal responding to T cells and enhancecytotoxicity of Dox against tumor cells			[120]
siLuc	Hepatocellular carcinoma	in vivo		Mice model		knockdown of Luc (siLuc)significant reductionin Luc activity for mice receiving NP-delivered siLuc treatments were confirmed by Luminescence imaging of the tumors confirming successfulsiRNA delivery and gene silencing			[121]
siPDL1	Pancreatic cancer	in vitro		PAN 02 cell line		Combination therapy consisting of gemcitabine and MN-siPDL1			[122]
		in vivo		and mice model		in a syngeneic murine pancreatic cancermodel resulted in a significant reduction in tumor growth and an increase in survival
PD-1 siRNA	skin cancer	in vitro		B16 cell line and		PD-1 siRNA delivered by attenuated			[123]
		in vivo		C57BL/6 mice		Salmonella to melanoma-bearing mice in combination with pimozide showed optimal therapeutic effect on melanoma
Si-ChLa NPs +Dendritic cell	breast cancer	in vivo		Mice		decreased tumor growth and metastasis ↓CD73 ↓Regulatory T ↓myeloid derived suppressor cells (MDSCs) ↓ and tumor associated macrophages ↑T cells, ↑inflammatory cytokines ↑interferon (IFN)-γ, ↑(IL)-17 ,↓IL-10			[124]
siRNA Targeting Notch1	Melanoma	in vitro		B16F1		↓cell proliferation			[125]
		in vivo		mice		↓ Notch1, ↓hey1, ↓tumor growth ↑tumor-infiltrating CD8+ T lymphocytes and IFN-γ
siIL-10RA+siTGF-βR	cervical cancer	in vitro		dendritic cell TC-1 P0 tumour model		initiated the strongest antigen-specific CD8(+) T cell immune responses			[126]
HPV Targetting	-	in vivo		C57BL/6 mice		reduced tumor growth			[127]
siRNA polyplex encapsulated in PLGA np	Melanoma	in vitro		DC		STAT3 silencing by nps restored DC maturation ↑CD86,↑TNF-α ↑T cell proliferation			[128]
Hsacirc0009361	colorectal cancer		in vitro in vivo		CRC tissues and cells Mice		↑expression of APC2 and inhibited the activity of the Wnt/β-catenin pathway by competitively combining with miR-582 inhibited the growth & metastasis of CRC	[129]
circCACTIN	Gastric cancer		In vitro		BGC-823,MGC-803		↑CircCACTIN expression Knockdown of circCACTIN inhibited GC cells proliferation migration, invasion	[130]
			In vivo		BAL/BC Mice model		circCACTIN up-regulation promoted GC tumor growth and EMT, and circCACTIN down-regulation inhibited GC tumor growth and EMT SGC-7901 cell line