Table 1.

Targeting WNT-β-catenin in cancer immunotherapy

Cancer type	Target regimen	Effects	References
NSCLC	WNT/β-catenin blockade plus anti-PD-1	Combination therapy better promoted anti-tumor immunity	[13]
MSS CRC	PORCN inhibitor ETC-159 plus anti-PD-1 (nivolumab)	Combination therapy in in mice engrafted tumor reduced tumor volume, increased the proportion of effector CD4+ and CD8+ T cells and reduced Treg population	[84]
Melanoma	ETC-159 plus anti-PD-1	Anti-PD-1 resistance is linked positively with increased WNT ligand signaling, and anti-PD-1 refractory melanoma is sensitive to the ETC-159 therapy	[30]
Advanced solid cancers	WNT974 plus anti-PD-1 (spartalizumab)	Combination therapy resulted in a stable disease in 53% of patients who were refractory to prior anti-PD-1, with uveal melanoma all cases had stable disease	[22]
HCC	Nanoparticle-based inhibition of β-catenin and PD-L1	Nanoparticle delivery increased intra-tumoral proportion and activity of CD8+ T cells, and it showed higher anti-tumor effects compared with anti-PD-L1 in orthotopic homograft animal model	[83]
Xenograft model	WNT inhibitors plus anti-PD-L1	WNT blockade increased anti-PD-L1 efficacy through hampering CAF-related immunotherapy resistance	[85]

MSS, microsatellite stable; CRC, colorectal cancer; PD-1, programmed death-1; Treg, regulatory T; HCC, hepatocellular carcinoma; PD-L1, programmed death-ligand 1; and CAF, cancer-associated fibroblast