{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:14:08Z","timestamp":1792181648797,"version":"4.4.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Department of Science and Technology of Jilin Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Adrenal tumors comprise a heterogeneous spectrum ranging from functional adenomas to aggressive adrenocortical carcinoma (ACC) and pheochromocytoma\/paraganglioma (PHEO\/PPGL) with metastatic potential. Although traditionally interpreted through hormone excess and oncogenic alterations, current evidence indicates that these tumors are endocrine-shaped immune ecosystems in which hormone secretion, molecular subtype, stromal architecture, metabolic stress, and immune infiltration interact to determine tumor behavior and therapeutic vulnerability. Across subtypes, distinct immune\u2013stromal states emerge: aldosterone-producing adenoma (APA) contains M2-polarized macrophages, specialized endothelial subsets, and metabolic heterogeneity; cortisol-producing adenoma (CPA) is characterized by local glucocorticoid-driven immunosuppression and altered macrophage and T-cell states; ACC is relatively immune-depleted and shaped by glucocorticoid signaling, hypoxia, senescence, and myeloid suppression; and PHEO\/PPGL exhibits subtype-dependent angiogenic and immune features linked to catecholamine biology and pseudohypoxia. The strongest human evidence supports cortisol-associated immune remodeling in CPA, macrophage-rich niches in APA, and immune ecotypes in ACC, whereas CAF-mediated immune exclusion, ion-channel-driven immune regulation, and several metabolite-based mechanisms remain largely extrapolative. Clinically, immune checkpoint blockade has shown modest and heterogeneous activity, especially in ACC, where PD-L1 and tumor mutational burden have not consistently predicted response, while selected PPGL subsets may be biologically more permissive. These findings support a model in which adrenal tumors should be classified not only by histology and hormone excess, but also by endocrine\u2013immune microenvironmental states, with implications for biomarker development and rational combination therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1853359","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:29Z","timestamp":1782452789000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Adrenal tumor microenvironment: hormone\u2013immune crosstalk, molecular heterogeneity, and immunotherapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Operating Room 1, the First Hospital of Jilin University","place":["Changchun, Jilin, 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