{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:53:00Z","timestamp":1767768780689,"version":"3.48.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Prostate cancer (PCa) remains a major health burden, and identifying target molecules will provide new research ideas for treating PCa.\n                      <jats:italic>TBX21<\/jats:italic>\n                      is a transcriptional factor with critical functions in tumor development, roles of which in PCa were studied herein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TBX21<\/jats:italic>\n                      expression was evaluated by RNA-seq, RT-PCR, Western blot, and immunohistochemistry in PCa tissues and cell lines. Functional assays were performed using LNCaP and 22RV1 cells with\n                      <jats:italic>TBX21<\/jats:italic>\n                      knockdown to assess proliferation and apoptosis. Tumor growth and immune alterations were examined in xenograft and humanized immune cell models, while flow cytometry and Western blot were used to characterize immune cell subsets and effector molecules.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TBX21<\/jats:italic>\n                      expression was significantly elevated in PCa tissues and cell lines.\n                      <jats:italic>TBX21<\/jats:italic>\n                      knockdown was associated with reduced proliferation and increased apoptosis\n                      <jats:italic>in vitro<\/jats:italic>\n                      and suppressed tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . In humanized xenografts,\n                      <jats:italic>TBX21<\/jats:italic>\n                      silencing was accompanied by a decrease in regulatory T cells (Treg) and an increase in Th17 and cytotoxic CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, together with enhanced expression of effector molecules (TNF-\u03b1, GZMB). Co-culture experiments showed that\n                      <jats:italic>TBX21<\/jats:italic>\n                      -deficient tumor cells reduced the induction of CD25\n                      <jats:sup>+<\/jats:sup>\n                      Foxp3\n                      <jats:sup>+<\/jats:sup>\n                      Treg cells from activated CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TBX21<\/jats:italic>\n                      is associated with tumor progression and an immunosuppressive microenvironment in PCa, underscoring its potential role in modulating the tumor\u2013immune balance.\n                    <\/jats:p>\n                  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