{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:03:11Z","timestamp":1790492591954,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_179394"],"award-info":[{"award-number":["310030_179394"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,8]]},"abstract":"<jats:p>\n                    Leukemia stem cells (LSCs) promote the disease and seem resistant to therapy and immune control. Why LSCs are selectively resistant against elimination by CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells (CTLs) is still unknown. In this study, we demonstrate that LSCs in chronic myeloid leukemia (CML) can be recognized and killed by CD8\n                    <jats:sup>+<\/jats:sup>\n                    CTLs in vitro. However, Tregs, which preferentially localized close to CD8\n                    <jats:sup>+<\/jats:sup>\n                    CTLs in CML BM, protected LSCs from MHC class I\u2013dependent CD8\n                    <jats:sup>+<\/jats:sup>\n                    CTL\u2013mediated elimination in vivo. BM Tregs in CML were characterized by the selective expression of tumor necrosis factor receptor 4 (Tnfrsf4). Stimulation of Tnfrsf4 signaling did not deplete Tregs but reduced the capacity of Tregs to protect LSCs from CD8\n                    <jats:sup>+<\/jats:sup>\n                    CTL\u2013mediated killing. In the BM of newly diagnosed CML patients,\n                    <jats:italic>TNFRSF4<\/jats:italic>\n                    mRNA levels were significantly increased and correlated with the expression of the Treg-restricted transcription factor\n                    <jats:italic>FOXP3<\/jats:italic>\n                    . Overall, these results identify Tregs as key regulators of immune escape of LSCs and TNFRSF4 as a potential target to reduce the function of Tregs and boost antileukemic immunity in CML.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.151797","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:55:14Z","timestamp":1635857714000},"source":"Crossref","is-referenced-by-count":41,"title":["Tnfrsf4-expressing regulatory T cells promote immune escape of chronic myeloid leukemia stem cells"],"prefix":"10.1172","volume":"6","author":[{"given":"Magdalena","family":"Hinterbrandner","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital,"},{"name":"Department for BioMedical Research (DBMR),"},{"name":"Graduate School of Cellular and Biomedical Sciences, 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