Figure 8.

PD-L1 expression is very positively associated with c-Myc or STAT3 expression in patients with various tumors, and a model for the mechanism is proposed. (A–C) Using IF analysis, we determined the protein expression of PD-L1 and c-Myc in TMAs of OvCa (A), invasive BCa (B), and HCC (C) specimens. Each tumor TMA slide was incubated with anti-PD-L1 or anti-c-Myc Abs and followed by specific fluorescent secondary Abs and IF analysis, as described previously. (D–F) We analyzed both PD-L1 versus STAT3 mRNA expression data in human primary ovarian tumor (D), breast tumor (E), and HCC tumor (F) tissues from the Cancer Genome Atlas (TCGA) datasets using cBioPortal.32 PD-L1 expression was positively associated with STAT3 expression in ovarian ad breast tumors. P values between the PD-L1 group versus the STAT3 group were shown. (G and H) We analyzed PD-L1 versus STAT3 and PD-L1 versus FOXO3 mRNA expression data in human primary pediatric neuroblastoma and stomach cancer tissues from TCGA datasets. P values between the tested groups were shown. (I) We analyzed PD-L1 versus FOXO3 mRNA expression data in various human primary tumor tissues (n=2158) from TCGA datasets. P values between the tested groups were shown. (J) A schema depicts a proposed model for the FOXO3-mediated blocking dual c-Myc-PDL1 and STAT3-PD-L1 pathways by SN-38 to promote NK or CD8+ T cell antitumor immunity. Abs, antibodies; BCa, breast cancer; HCC, hepatocellular carcinoma; IF, immunofluorescence; NK, natural killer; OvCa, PD-L1, programmed death-ligand 1; TMA, tissue microarray.