{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:24:08Z","timestamp":1793665448969,"version":"4.5.1"},"reference-count":82,"publisher":"American Society for Clinical Investigation","issue":"21","funder":[{"name":"Leukemia and Lymphoma Society","award":["LLS TRP #6449-13"],"award-info":[{"award-number":["LLS TRP #6449-13"]}],"id":[{"id":"https:\/\/ror.org\/04m0xav37","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UM1 CA186691"],"award-info":[{"award-number":["UM1 CA186691"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL110907-01"],"award-info":[{"award-number":["R01 HL110907-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"American Society for Blood and Marrow Transplantation","award":["New Investigator Award\/Gabrielle\u2019s Angel Foundation"],"award-info":[{"award-number":["New Investigator Award\/Gabrielle\u2019s Angel Foundation"]}],"id":[{"id":"https:\/\/ror.org\/018et4y07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Vienna Fund for Innovative Cancer Research","award":["Research Development Award"],"award-info":[{"award-number":["Research Development Award"]}]},{"DOI":"10.13039\/501100003748","name":"Swedish Society for Medical Research","doi-asserted-by":"crossref","award":["Fellowship for Postdoctoral scholars in Medical Science"],"award-info":[{"award-number":["Fellowship for Postdoctoral scholars in Medical Science"]}],"id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001388","name":"Wenner-Gren Foundation","doi-asserted-by":"crossref","award":["Postdoctoral scholarship"],"award-info":[{"award-number":["Postdoctoral scholarship"]}],"id":[{"id":"10.13039\/100001388","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,2]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Our understanding of phenotypic and functional signatures of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysfunction in acute myeloid leukemia (AML) is limited. Deciphering these deranged T cell functional states and how they are impacted by induction chemotherapy is essential for incorporation of novel immune-based strategies to restore and maintain antileukemia immunity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We utilized high-dimensional immunophenotyping, gene expression, and functional studies to characterize peripheral blood and bone marrow CD8\n                    <jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:sup>\n                    T cells in 72 AML patients at diagnosis and after induction chemotherapy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Our data suggest that multiple aspects of deranged T cell function are operative in AML at diagnosis, with exhaustion and senescence being the dominant processes. Following treatment, the phenotypic and transcriptional profile of CD8\n                    <jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:sup>\n                    T cells diverged between responders and nonresponders. Response to therapy correlated with upregulation of costimulatory, and downregulation of apoptotic and inhibitory, T cell signaling pathways, indicative of restoration of T cell function. In functional studies, AML blasts directly altered CD8\n                    <jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:sup>\n                    T cell viability, expansion, co-signaling and senescence marker expression. This CD8\n                    <jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:sup>\n                    T cell dysfunction was in part reversible upon PD-1 blockade or OX40 costimulation in vitro.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    Our findings highlight the uniqueness of AML in sculpting CD8\n                    <jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:sup>\n                    T cell responses and the plasticity of their signatures upon chemotherapy response, providing a compelling rationale for integration of novel immunotherapies to augment antileukemia immunity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    This work was supported by the Leukemia\n                    <jats:bold>&amp;<\/jats:bold>\n                    Lymphoma Society grant no. 6449-13; NIH grants UM1-CA186691 and R01-HL110907-01; the American Society for Blood and Marrow Transplantation New Investigator Award\/Gabrielle\u2019s Angel Foundation; the Vienna Fund for Innovative Cancer Research; and by fellowships from the Wenner-Gren Foundation and the Swedish Society for Medical Research.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.120974","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T11:01:23Z","timestamp":1541070083000},"source":"Crossref","is-referenced-by-count":199,"title":["Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy"],"prefix":"10.1172","volume":"3","author":[{"given":"Hanna A.","family":"Knaus","sequence":"first","affiliation":[{"name":"Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA."},{"name":"Division of Hematology and 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