Immune checkpoint blockade as an accelerator of adrenal aging: a testable model linking low-grade cortical inflammation to proteostasis failure, LDLR/SULT2A1 suppression, and reduced DHEA output

<p>Immune checkpoint blockade (ICB) unleashes antitumor immunity but frequently provokes enduring endocrine toxicities. We hypothesize that ICB accelerates adrenal aging by establishing chronic low-level inflammation within the adrenal cortex, with targeting vulnerability of the zona reticularis. Integrating a recently published human multiorgan aging proteome atlas and primate adrenal aging study with survivorship data after ICB therapy, we propose a testable…