{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:28:59Z","timestamp":1793276939185,"version":"4.5.0"},"reference-count":115,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI20\/00184"],"award-info":[{"award-number":["FI20\/00184"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto de Salud Carlos III (ISCIII), co-funded by the European Regional Development Fund\/European Social Fund","award":["PI19\/00083"],"award-info":[{"award-number":["PI19\/00083"]}]},{"name":"Roche Foundation Research Grant","award":["None"],"award-info":[{"award-number":["None"]}]},{"name":"Ministerio de Econom\u00eda, Industria y Competitividad (MINECO)","award":["CIBERONC CB16\/12\/00291"],"award-info":[{"award-number":["CIBERONC CB16\/12\/00291"]}]},{"name":"Direcci\u00f3n General de Universidades e Investigaci\u00f3n Consejer\u00eda de Educaci\u00f3n e Investigaci\u00f3n de la Comunidad de Madrid","award":["B2017\/BMD-3778"],"award-info":[{"award-number":["B2017\/BMD-3778"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The classic Hodgkin lymphoma (cHL) tumor microenvironment (TME) is by far the most abundant component of tumors and is responsible for most of their biological and clinical characteristics. Recent advances in our knowledge of these networks in cellular interactions allow us to understand that the neoplastic Hodgkin and Reed Sternberg (HRS) cells, although they are in the minority, are the main architects of this dysregulated immune milieu. Here, we review the major changes that have happened in recent years: from TME as a helpless bystander, reflecting an ineffective immune response, to a dynamic tumor-promoting and immunosuppressive element. The HRS cells promote survival through interconnected intrinsic and extrinsic alterations, boosting pro-tumoral signaling pathways through genetic aberrations and autocrine growth signals, in parallel with abnormal cytokine secretion for the recruitment and selection of the best cell partners for this immunosuppressive TME. In turn, cHL is already proving to be the perfect model with which to address an immune checkpoint blockade. Preliminary data demonstrate the utility of druggable key signaling pathways in this ensemble, such as JAK-STAT, NF-\u03baB, and others. In addition, myriad biomarkers predicting a response await validation by new in situ multiplex analytical methods, single-cell gene expression, and other techniques. Together, these components will define the functional phenotypes with which we will elucidate the molecular pathogenesis of the disease and improve the survival of patients who are refractory to conventional therapies.<\/jats:p>","DOI":"10.3390\/cancers14051360","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:35:37Z","timestamp":1646742937000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The Hodgkin Lymphoma Immune Microenvironment: Turning Bad News into Good"],"prefix":"10.3390","volume":"14","author":[{"given":"Victoria","family":"Men\u00e9ndez","sequence":"first","affiliation":[{"name":"Translational Research, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Sol\u00f3rzano","sequence":"additional","affiliation":[{"name":"Pathology Department, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Translational Research, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Montalb\u00e1n","sequence":"additional","affiliation":[{"name":"Hematology Department, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-0806","authenticated-orcid":false,"given":"Juan F.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Pathology Department, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Opinto, G., Agostinelli, C., Ciavarella, S., Guarini, A., Maiorano, E., and Ingravallo, G. 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