Figure 1.

MerTK mediates HCC resistant to anti-PD-L1 treatment

(A) Schematic illustrating the establishment of anti-PD-L1-resistant strains in vivo.

(B) Tumor growth curves of subcutaneous implantation models in Hepa1-6 and Res1-6 strains treated with anti-PD-L1 (aPD-L1) or IgG.

(C) Survival of orthotopic implantation models of Hepa1-6 and Res1-6 strains treated with aPD-L1 or IgG.

(D) Proteomic sequencing analysis was used to analyze the differently expressed proteins in Hepa1-6 and Res1-6. The top 20 differently expressed proteins are presented in a heatmap, including 10 upregulated and 10 downregulated proteins.

(E) Western blot of p-MerTK, MerTK, and β-actin in Hepa1-6, Res1-6, HCA-1, and Res-CA1 strains.

(F) IHC staining of p-MerTK and MerTK in Hepa1-6 and Res1-6 subcutaneous tumor tissues.

(G) Locations of sensitive and resistant tumors were exhibited by MRI, and AFP values before and after anti-PD-L1/PD-1 therapy between patient in sensitive group and patient in resistant group. IHC staining of MerTK expression in HCC tissues from sensitive and resistant patients received anti-PD-1/PD-L1 therapy.

(H and I) Subcutaneous xenograft mouse model of Res1-6, Res1-6-sh-MerTK, Hepa1-6, and Hepa1-6-OE-MerTK strains treated with anti-PD-L1 or IgG. When the tumor volume approximately reached 100 mm³ in size, tumor volume was measured every 3 days. After 25 days of treatment, mice were sacrificed. Shown are tumor appearance and tumor growth curves.

All results are shown as mean ± SEM (n = 5). One- or two-way ANOVA was used to analyze the data; ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.