The Immune Biology of the Adrenal Gland Microenvironment and Its Role in Metastatic Progression

Metastatic lesions are the most common malignant tumor of the adrenal gland. While surgery can have a favorable surgical outcome for isolated adrenal metastatic lesions, most adrenal metastases occur in the context of disseminated disease, and the overall prognosis remains poor. Although data are limited, metastatic lesions from diverse solid tumors to the adrenal gland have typically demonstrated poor response to immunotherapy, particularly immune checkpoint inhibitors with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade. This apparent resistance to immunotherapy suggests that the adrenal gland microenvironment may be influenced by local microenvironmental factors, resulting in an organ microenvironment that is immune tolerant and permissive to tumor growth. However, the current literature on the adrenal gland immune microenvironment is limited, underscoring the need for better understanding of the immunobiology of this critical endocrine organ. Thus, the current scarcity of scientific studies on this topic is a novel opportunity to investigate and develop innovative treatment strategies for adrenal solid cancer metastases. In this literature review, we summarize the available data published on the immunobiology of the adrenal gland and the potential local immune mechanisms that may be contributing to the adrenal gland's role in promoting resistance to otherwise breakthrough immunotherapy treatments.