β-Catenin-driven adrenocortical carcinoma is characterized with immune exclusion.

AIM

Adrenocortical carcinoma (ACC) is characterized by overexpressed , which is reported to modulate immune exclusion. Cross talk between and cancer immunity in ACC remains unclear.

MATERIALS AND METHODS

In silico reproduction of TCGA-ACC dataset (N = 92) and external validation using tissue samples were performed (N = 16). Expression data of , PD-1, and PD-L1 were extracted in silico and tumor-infiltrating lymphocytes (TILs) were profiled using code provided by Tumor IMmune Estimation Resource (TIMER). In-house formalin-fixed paraffin-embedded ACC samples were processed using immunohistochemical (IHC) staining for , CD45, PD-1, and PD-L1.

RESULTS

Increased expression was significantly associated with worsened overall survival (OS) ( = 0.006). CD8 cells were significantly associated with better OS ( = 0.02). Higher PD-L1 ( = 0.019), but not PD-1 expression ( = 0.325), was associated with better OS. overexpression was significantly associated with increased tumor purity ( = 0.356, = 0.002) and fewer TILs ( = -0.833, = 0.029), decreased infiltrating CD8 cells ( = 0.033), and increased infiltrating B cells ( = 0.026). expression was negatively correlated with PD-L1 expression ( = -0.308, = 0.006) but not with PD-1 expression ( = 0.067), which were externally validated ( = 0.032 for PD-L1 and = 0.400 for PD-1). The Cox regression model encompassing gender, B cells, CD8 cells, PD-L1, CTNNB1, and Ki-67 revealed that only Ki-67 overexpression remained significantly associated with OS ( < 0.001), while showed marginal significance ( = 0.06). -overexpressed patients were more likely to have cortisol excess ( = 0.003).

CONCLUSION

ACC with CTNNB1 overexpression is associated with poor prognosis and decreased immunity. Our findings suggest that CTNNB1-targeting therapy may overcome immune exclusion in ACC.