{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T01:31:03Z","timestamp":1793669463382,"version":"4.5.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hodgkin lymphoma (HL) is characterized by rare Hodgkin\/Reed-Sternberg (H\/RS) cells surrounded by a predominant immune infiltrate that shapes tumor biology and influences prognosis. FKBP51, an immunophilin and NF-\u03baB\/Akt modulator, is implicated in cancer progression, but its role within the HL tumor microenvironment (TME) remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 103 HL cases by immunohistochemistry for FKBP51, Bcl2, and immune subsets (CD4, CD8, CD68, CD163), with quantitative PCR of\n                      <jats:italic>FKBP5, TRAF2, PCNA, XIAP<\/jats:italic>\n                      , and\n                      <jats:italic>BCL2<\/jats:italic>\n                      in 36 cases. Spatial immune architecture was assessed morphologically and via image analysis, with a focus on CD4 T-cell rosettes. Prognostic associations were evaluated through multivariate analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FKBP51 was detected in both H\/RS cells and infiltrating lymphocytes. While nuclear FKBP51 in H\/RS cells lacked prognostic significance, FKBP51 expression in the TME correlated with adverse outcomes and remained an independent prognostic factor. CD4 T cells were the predominant immune cell subset and the main FKBP51-positive population. However, it was the density of tumor-associated macrophages (TAMs), rather than CD4 T-cell density, that held prognostic significance. CD4 T cells frequently formed rosette-like structures around H\/RS cells, a spatial organization associated with the highest FKBP51 scores and unfavorable prognosis. CD8 T cells were less abundant, increased in advanced stages along with TAMs, and exhibited limited FKBP51 expression. Gene expression analysis showed FKBP51 correlation with proliferative and anti-apoptotic transcripts (\n                      <jats:italic>PCNA, TRAF2, XIAP<\/jats:italic>\n                      ), supporting a protumor, NF-\u03baB-driven microenvironment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FKBP51 expression in CD4 tumor-infiltrating lymphocytes, rather than tumor cells, defines a protumor TME that supports H\/RS cell survival. Spatial immune architecture, particularly CD4 rosettes and TAM density, holds prognostic relevance in HL. FKBP51 may serve as a biomarker for risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1604920","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:23:59Z","timestamp":1762151039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression and prognostic value of FKBP51 in Hodgkin 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