{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:53:41Z","timestamp":1793836421844,"version":"4.6.1"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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:p>Post-transplant lymphoproliferative disorder (PTLD) in kidney transplantation is increasingly recognized not merely as a passive consequence of systemic immunosuppression, but as a malignancy driven by an actively engineered, immunosuppressive tumor microenvironment (TME). This review explores the sophisticated mechanisms by which Epstein-Barr Virus (EBV) remodels the local cellular landscape, detailing how the viral oncoprotein LMP1 acts as a master regulator to upregulate immune checkpoints like PD-L1 and orchestrate the recruitment of M2-polarized macrophages and regulatory T cells. We further highlight the emerging role of extracellular vesicles (exosomes) as vesicles for viral microRNAs, enabling the tumor to condition immune cells at a distance and establish a tolerogenic niche. These viral strategies are contrasted with the distinct pathogenesis of late-onset, EBV-negative PTLD, which relies on genomic instability rather than viral immunomodulation. Finally, we evaluate how this deepened understanding of the TME is transforming therapeutic paradigms, moving from standard reduction of immunosuppression toward targeted interventions, such as EBV-specific adoptive T-cell therapies (Tabelecleucel) and CAR-T cells, designed to dismantle the tumor\u2019s protective architecture while minimizing the high risk of allograft rejection associated with checkpoint inhibitors.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1774164","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:25:09Z","timestamp":1775535909000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The immunosuppressive tumor microenvironment in post-transplant lymphoproliferative disorder: pathogenesis and novel therapeutic frontiers"],"prefix":"10.3389","volume":"17","author":[{"given":"Andrea","family":"Dello Strologo","sequence":"first","affiliation":[{"name":"Department of Nephrology and Dialysis, Azienda USL Roma 6","place":["Albano Laziale, Italy"]},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"De Liso","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scarsella","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Trotta","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, 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