Impact of steroid differentiation on tumor microenvironment revealed by single-nucleus atlas of adrenal tumors.

ABSTRACT: Adrenocortical carcinomas (ACC) are aggressive and resistant to medical treatment. This study reports a single-nucleus transcriptome atlas of steroid and microenvironment cells in 38 human normal adrenals and adrenocortical tumors. We identify intermediate-state cells between glomerulosa and fasciculata, a transition state in the centripetal trans-differentiation of normal steroid cells. In tumors, steroid cells show expression programs reflecting this zonation. Although ACC microenvironment is scarce, its signatures combine with those of steroid cells into ecotypes. A first ecotype combines cancer-associated fibroblasts, tumor-associated endothelial cells, with hypoxia and mitosis signatures in steroid cells. Another ecotype combines exhausted T cells, with fasciculata steroid signature.

SUBMITTER: Jouinot A 

PROVIDER: S-EPMC12501071 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature