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However, the immunosuppressive tumor microenvironment limits \u03b3\u03b4T-cell effector function and promotes immune evasion. In this study, we found that ULBP1 expression was frequently down-regulated in NB tumor tissues and cell lines and that low ULBP1 expression was associated with high-risk clinical features and poor prognosis. Further investigation revealed that doxorubicin, a key chemotherapeutic agent used in NB treatment, up-regulated ULBP1 through down-regulating DNA methyltransferase 1 (DNMT1), thereby decreasing methylation of the ULBP1 promoter. This epigenetic modulation sensitized NB tumor cells to \u03b3\u03b4T-cell\u2013mediated cytotoxicity in vitro and in vivo. Collectively, our findings uncover a novel mechanism by which doxorubicin enhances NB tumor susceptibility to \u03b3\u03b4T-cell\u2013mediated killing through ULBP1 up-regulation. This study provides a strong rationale for combining chemotherapy with \u03b3\u03b4T-cell\u2013based immunotherapy to improve outcomes in high-risk NB patients.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag144","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:02:53Z","timestamp":1781740973000},"source":"Crossref","is-referenced-by-count":0,"title":["Increased ULBP1 by doxorubicin sensitizes neuroblastoma to \u03b3\u03b4T-cell cytotoxicity"],"prefix":"10.1093","volume":"215","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health , Beijing,","place":["China"]},{"name":"Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center 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