Adrenocortical carcinoma (ACC) — a rare cancer of the outer layer of the adrenal gland — is one of the most aggressive cancers and has limited therapeutic options when it cannot be surgically removed. About half of ACC patients have excess steroid hormone secretion, primarily cortisol, which has immunosuppressive effects and appears to contribute to failure of immunotherapies.
To gain insights for therapeutic development, Naira Baregamian, MD, and colleagues profiled immune-related gene expression in the ACC tumor microenvironment. They compared patients with cortisol-secreting or non-secreting ACC using The Cancer Genome Atlas database.
The findings, reported in the Journal of Cellular and Molecular Medicine, demonstrate differentially expressed immune genes and tumor-infiltrating immune cell profiles in the two types of ACC and identified elevated expression levels of CCRL2 encoding a chemokine scavenging receptor in cortisol-secreting ACC.
The immunosuppressive profile in cortisol-secreting ACC has a direct impact on patient survival, the researchers report. They identified prognostic indicators and potential targets in the ACC tumor microenvironment that may guide strategies to treat poorly responsive cortisol-secreting ACC.
Joining Baregamian on the study were Jordan Baechle, MD, David Hanna, MD, Konjeti Sekhar, PhD, Jeffrey Rathmell, PhD, and W. Kimryn Rathmell, MD, PhD.