Immunotherapy failure in adrenocortical cancer: where next?

Abstract

Immunotherapy is widely used in the treatment of different cancer types, including metastatic melanoma, non-small cell lung cancer, renal cell carcinoma and urothelial cancer. The results of the phase I JAVELIN study failed to demonstrate a substantial activity of the PDL-1 inhibitor Avelumab in advanced adrenocortical carcinoma (ACC). This editorial focus on the possible mechanisms of ACC immunoevasion and suggests strategies to overcome the intrinsic immunotherapy resistance of this disease.

Figure 1

Mechanisms of ACC immunoresistance. The upregulation of β-catenin reduces production of different chemokines (such as CCL4, BATF Dcs, CXCL10) leading to the lack of T cell priming and the consequent recruitment of effector T cells in the tumor. TP53‐mutated tumor cells lack production of key chemokines required for the recruitment of natural killer cells and T cells, which results in exclusion of effector T cell from the tumor infiltration. Low PD-L1 expression and increased production of steroids can impair tumor immunogenicity. BATF DC, basic leucine zipper transcriptional factor ATF-like 3 lineage dendritic cells; CCL, CC-chemokine ligand; CXCL, CXC-chemokine ligand; PD-L1, programmed cell death 1 ligand 1.