{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:13:34Z","timestamp":1792815214080,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["21JR11RA104"],"award-info":[{"award-number":["21JR11RA104"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>BCL\u20102<\/jats:italic> is one of the key genes in the mitochondrial apoptotic pathway, and BCL\u20102 inhibitor Venetoclax (VEN) is the preferred targeted drug for acute myeloid leukemia (AML) patients. However, the effects of VEN on immune cells and antitumor immune responses in AML patients are poorly understood. We first tested the influence of VEN on AML cells and immune cells. Subsequently, we sorted CD4+ T cells and CD8+ T cells from newly diagnosed AML patients in\u00a0vitro and constructed a peripheral blood mononuclear cell (PBMC)\u2010humanized AML mouse model to explore the effects of VEN on the T cell number, function, and antitumor immune responses, while actively seeking potential mechanisms. VEN could effectively induce leukemia cell apoptosis and affect the lymphocyte proportion and cytokine levels in the tumor immune microenvironment of AML. T cells of AML patients had apoptosis resistance to VEN, possibly due to their relatively low expression levels of BCL\u20102 protein. VEN could regulate the secretory function and activation status of T cells in AML, which mainly manifested in promoting IFN\u2010\u03b3 and Perforin and Granzyme B secretion, upregulating PD\u20101 expression, promoting T cell activation, and increasing the proportion of memory T cells. Finally, it was also observed that VEN could enhance T cell\u2010mediated antitumor immune responses in AML. Mechanistically, VEN modulates the glycolysis pathway of T cells to regulate their number, function, and antitumor immune responses. This research provided a new perspective that molecular\u2010targeted drugs can promote tumor cell death through a unique immune\u2010dependent mechanism.<\/jats:p>","DOI":"10.1111\/cas.70139","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T07:34:11Z","timestamp":1754552051000},"page":"2657-2676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>BCL<\/scp>\u20102 Inhibitor Regulates Number, Function, and Antitumor Immunity of T Cells by Influencing Glycolysis in <scp>AML<\/scp>"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-544X","authenticated-orcid":false,"given":"Xiaohuan","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Hematology, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"},{"name":"Gansu Clinical Medical Research Center of Hematology (National Sub\u2010Center), The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Hematology of Gansu Province, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futian","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment Oncology of Gansu Province, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Tumor Surgery, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Hematology of Gansu Province, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"},{"name":"Gansu Clinical Medical Research Center of Hematology (National Sub\u2010Center), The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"},{"name":"Key Laboratory of the Hematology of Gansu Province, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liansheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"},{"name":"Gansu Clinical Medical Research Center of Hematology (National Sub\u2010Center), The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"},{"name":"Key Laboratory of the Hematology of Gansu Province, The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620719860645"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009010"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-379081"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2021.101251"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01348-8"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.031"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31896"},{"key":"e_1_2_13_9_1","article-title":"Chemotherapy Induces Myeloid\u2010Driven Spatial T\u2010Cell Exhaustion in Ovarian Cancer","volume":"20","author":"Hynninen J.","year":"2024","journal-title":"bioRxiv"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0759"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04285-4"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2017.10.001"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.670324"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxab077"},{"key":"e_1_2_13_15_1","first-page":"98","article-title":"Bcl\u20102 Oncoprotein Expression in Acute Myeloid Leukemia","volume":"80","author":"Bensi L.","year":"1995","journal-title":"Haematologica"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2019.1627327"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.11.015"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00870-3"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0590-1"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI152673"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.661939"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34566"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.02.005"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14040288"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2023.2219554"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2016.08.002"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009499"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689720945682"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05937-3"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.27573"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-018-2652-2"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T10:35:33Z","timestamp":1759314933000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/cas.70139"],"URL":"https:\/\/doi.org\/10.1111\/cas.70139","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"2025-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}