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The TME of cHL critically depends on immune cells to support tumor growth as H\u2010RS cells cannot survive and proliferate in isolation.<\/jats:p><jats:p><jats:bold>Recent Findings:<\/jats:bold> Programmed cell death protein 1 (PD\u20101) ligand expressed on H\u2010RS cells inhibits the clearance of tumor by causing T\u2010cell exhaustion. Nivolumab and pembrolizumab, PD\u20101 inhibitors, have been proven to be effective in treating adult and pediatric patients with R\/R cHL. Tumor\u2010associated macrophages (TAMs) are a central component of TME and are known to cause poor prognosis in adult HL. However, the prognostic impact of CD68+ TAMs in pediatric HL remains ambiguous. EBV modulates the tumor milieu of HL and plays a strategic role in immune escape by enrichment of the TME with <jats:italic>T<\/jats:italic><jats:sub><jats:italic>reg<\/jats:italic><\/jats:sub> cells and associated immunosuppressive cytokines in adult HL. In contrast, EBV+ pediatric patients have increased infiltration of CD8<jats:sup>+<\/jats:sup> T\u2010cells and show a better therapeutic response suggesting viral\u2010related TME is distinct in childhood HL. The role of CASP3 in apoptosis of H\u2010RS cells and its correlation with response prediction in adult and pediatric HL suggest it may serve as a potential biomarker. In cHL, CD30, EBV, and NF\u2010\u03baB signaling employ exosomes for cell\u2013cell communication that triggers the migration capacity of fibroblasts, stimulate to produce proinflammatory cytokines, and help to create a tumor\u2010supportive microenvironment.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The cHL microenvironment is distinct in adult and pediatric HL. Future studies are required to understand the role of interplay between H\u2010RS cells and EBV\u2010associated microenvironment and their clinical outcome. They may present novel therapeutic targets for the development of antilymphoma therapy.<\/jats:p>","DOI":"10.1002\/cnr2.1311","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T13:54:38Z","timestamp":1603720478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profile, <scp>EBV<\/scp>, and exosomes"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-2169","authenticated-orcid":false,"given":"Poonam","family":"Nagpal","sequence":"first","affiliation":[{"name":"College of Natural, Applied, and Health Sciences Kean University  Union New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante B.","family":"Descalzi\u2010Montoya","sequence":"additional","affiliation":[{"name":"Center for Discovery and 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