{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:02:29Z","timestamp":1791874949627,"version":"4.3.4"},"reference-count":357,"publisher":"The Endocrine Society","issue":"4","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z1AHD008735"],"award-info":[{"award-number":["Z1AHD008735"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues and extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can provide essential knowledge for the development of better therapeutic and tumor management strategies, especially for those with advanced and metastatic PPGLs. The first part of this review outlines the fundamental principles of the immune system and tumor microenvironment, and their role in cancer immunoediting, particularly emphasizing PPGLs. We focus on how the unique pathophysiology of PPGLs, such as their high molecular, biochemical, and imaging heterogeneity and production of several oncometabolites, creates a tumor-specific microenvironment and immunologically \u201ccold\u201d tumors. Thereafter, we discuss recently published studies related to the reclustering of PPGLs based on their immune signature. The second part of this review discusses future perspectives in PPGL management, including immunodiagnostic and promising immunotherapeutic approaches for converting \u201ccold\u201d tumors into immunologically active or \u201chot\u201d tumors known for their better immunotherapy response and patient outcomes. Special emphasis is placed on potent immune-related imaging strategies and immune signatures that could be used for the reclassification, prognostication, and management of these tumors to improve patient care and prognosis. Furthermore, we introduce currently available immunotherapies and their possible combinations with other available therapies as an emerging treatment for PPGLs that targets hostile tumor environments.<\/jats:p>","DOI":"10.1210\/endrev\/bnae005","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T17:02:49Z","timestamp":1708362169000},"page":"521-552","source":"Crossref","is-referenced-by-count":28,"title":["The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives"],"prefix":"10.1210","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-9822","authenticated-orcid":false,"given":"Ondrej","family":"Uher","sequence":"first","affiliation":[{"name":"Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892-1109 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Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) , Madrid 28029 ,","place":["Spain"]},{"name":"Familiar Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-5902","authenticated-orcid":false,"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) , Madrid 28029 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III (ISCIII) , Madrid 28029 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