Objective:

To detail the cellular and acellular components of the adrenal tumor microenvironment (TME), examine how molecular heterogeneity and hormone biology shape immune-stromal states, and assess immunotherapeutic opportunities.

Approach:

• Method: label
• Method: text

Key Findings:

• Adrenal tumors exhibit clinical heterogeneity, ranging from benign adenomas to aggressive carcinomas.
• The adrenal TME is characterized by interactions between hormone secretion and immune function, influencing tumor behavior and therapeutic response.
• Distinct immune-stromal states are observed across different tumor types: APA has M2-polarized macrophages, CPA shows local glucocorticoid-driven immunosuppression, ACC is immune-depleted, and PHEO/PPGL has subtype-dependent features.
• Cortisol-associated immune remodeling is notably supported in CPA, while immune checkpoint blockade has shown modest activity in ACC.

Interpretation:

Adrenal tumors should be classified by their endocrine-immune microenvironmental states, which has implications for biomarker development and combination therapies.

Limitations:

• Most studies are small and retrospective, limiting the understanding of the adrenal TME.
• Causal links between hormonal outputs and immune phenotypes are rarely demonstrated directly in human adrenal tumors.

Conclusion:

The review emphasizes the need for a deeper understanding of the adrenal TME and its implications for immunotherapy.