{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:15:46Z","timestamp":1788520546972,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A recent breakthrough therapy combining the BCL\u20102 inhibitor venetoclax with hypomethylating agents (HMAs) targeting DNA methyltransferase has improved outcomes for patients with acute myeloid leukemia (AML), but the responses and long\u2010term survival in older\/unfit patients and in patients with relapsed\/refractory AML remain suboptimal. Recent studies showed that inhibition of BCL\u20102 or DNA methyltransferase modulates AML T\u2010cell immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By using flow cytometry and time\u2010of\u2010flight mass cytometry, the authors examined the effects of the HMA decitabine combined with the BCL\u20102 inhibitor venetoclax (DAC\/VEN therapy) on leukemia cells and T cells in patients with AML who received DAC\/VEN therapy in a clinical trial. The authors investigated the response of programmed cell death protein 1 (PD\u20101) inhibition in the DAC\/VEN\u2013treated samples in vitro and investigated the triple combination of PD\u20101 inhibition with HMA\/venetoclax in the trial patients who had AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DAC\/VEN therapy effectively targeted leukemia cells and upregulated the expression of the immune checkpoint\u2010inhibitory receptor PD\u20101 in T cells while preserving CD4\u2010positive and CD8\u2010positive memory T cells in a subset of patients with AML who were tested. In vitro PD\u20101 inhibition potentiated the antileukemia response in DAC\/VEN\u2013treated AML samples. The combined use of azacitidine, venetoclax, and nivolumab eliminated circulating blasts and leukemia stem cells\/progenitor cells and expanded the percentage of CD8\u2010positive memory T cells in an illustrative patient with relapsed AML who responded to the regimen in an ongoing clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Immunomodulation by targeting PD\u20101 enhances the therapeutic effect of combining an HMA and venetoclax in patients with AML.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34566","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T12:56:05Z","timestamp":1670417765000},"page":"531-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Triple combination targeting methyltransferase, BCL\u20102, and PD\u20101 facilitates antileukemia responses in acute myeloid leukemia"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2207-9584","authenticated-orcid":false,"given":"Zhihong","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Leukemia Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-538X","authenticated-orcid":false,"given":"Abhishek","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Leukemia Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Herbrich","sequence":"additional","affiliation":[{"name":"Department of Leukemia Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas 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