{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:16:02Z","timestamp":1791414962006,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T00:00:00Z","timestamp":1324425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Classical Hodgkin lymphoma (cHL) is characterized by a small number of neoplastic cells in a background of reactive cells. Children and adults differ in constitution and functionality of the immune system and it is possible that there may be age\u2010related differences in tumor microenvironment composition in cHL. One hundred children with pediatric cHL were studied. Tumor\u2010infiltrating lymphocytes were analyzed by immunohistochemistry (IHC) and image analysis. Epstein\u2010Barr virus (EBV) status was determined by EBER\u2010specific <jats:italic>in situ<\/jats:italic> hybridization and IHC. Results were analyzed in the context of age\u2010group, histological characteristics and clinical follow\u2010up. EBV\u2010status was not associated with age\u2010group. Children &lt;10 years and EBV+ cases were characterized by a more intense T cell infiltrate, exhibiting a cytotoxic\/Th1 profile, characterized by higher numbers of CD3+, CD8+, TIA1+ and TBET+ lymphocytes. Extranodal disease (<jats:italic>p<\/jats:italic> = 0.016) and high number of GranzymeB+ lymphocytes (<jats:italic>p<\/jats:italic> = 0.04) were independently associated with reduced progression\u2010free survival (PFS). Yet, in EBV+ cases, improved outcome was observed in cases with low numbers of FOXP3+ lymphocytes (<jats:italic>p<\/jats:italic> = 0.046), FOXP3\/CD8 ratio &lt; 1 (<jats:italic>p<\/jats:italic> = 0.021) and TBET\/CMAF ratio &lt; 1 (<jats:italic>p<\/jats:italic> = 0.017). By contrast, in EBV\u2212 cases, poor survival was observed in cases with extranodal disease (<jats:italic>p<\/jats:italic> = 0.028), MC subtype (<jats:italic>p<\/jats:italic> = 0.009) and high numbers of TIA1+ (<jats:italic>p<\/jats:italic> = 0.044) and GranzymeB+ (<jats:italic>p<\/jats:italic> = 0.04) lymphocytes. The results suggest that in EBV+ cHL an effective immune response directed against viral or tumor antigens may be triggered in the tumor microenvironment and that physiological and age\u2010related changes of the immune system may also modulate the tumor microenvironment in pediatric cHL.<\/jats:p>","DOI":"10.1002\/ijc.27314","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T05:55:59Z","timestamp":1319522159000},"page":"1142-1152","source":"Crossref","is-referenced-by-count":66,"title":["Tumor microenvironment composition in pediatric classical Hodgkin lymphoma is modulated by age and Epstein\u2010Barr virus infection"],"prefix":"10.1002","volume":"131","author":[{"given":"M\u00e1rio Henrique M.","family":"Barros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Vera\u2010Lozada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Niedobitek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,21]]},"reference":[{"key":"e_1_2_5_2_2","volume-title":"International Agency for Research on Cancer., World Health Organization. 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