{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:11:33Z","timestamp":1788383493199,"version":"build-2803163510"},"reference-count":29,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of Texas MD Anderson Cancer Center Support Grant","award":["CA016672"],"award-info":[{"award-number":["CA016672"]}]},{"name":"University of Texas MD Anderson\u2013China Medical University and Hospital Sister Institution Network Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Advanced Scholar Program at MD Anderson","award":["2018-2019, Koller"],"award-info":[{"award-number":["2018-2019, Koller"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,8,4]]},"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism of immune escape in patients with acute myeloid leukemia after HSCT. Here we report that treatment with the tyrosine kinase inhibitor, dasatinib, and an anti-PD-1 antibody in preclinical models of Philadelphia chromosome positive B-cell acute lymphoblastic leukemia is highly active. The dasatinib and anti-PD-1 combination reduces tumor burden, is efficacious, and extends survival. Mechanistically, we found that treatment with dasatinib significantly increased MHC II expression on the surface of antigen-presenting cells (APC) in a tumor microenvironment-independent fashion and caused influx of APC cells into the leukemic bone marrow. Finally, the induction of MHC II may potentiate immune memory by impairing leukemic engraftment in mice previously cured with dasatinib, after re-inoculation of leukemia cells. In summary, our data suggests that anti-PD-1 therapy may enhance the killing ability of dasatinib via dasatinib driven APC growth and expansion and upregulation of MHC II expression, leading to antileukemic immune rewiring.<\/jats:p>","DOI":"10.1136\/jitc-2022-006619","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T14:30:24Z","timestamp":1696429824000},"page":"e006619","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["PD-1 blockade in combination with dasatinib potentiates induction of anti-acute lymphocytic leukemia immunity"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04329325","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02744768","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03263572","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02143414","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03147612","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03160079","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03512405","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02879695","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-5320","authenticated-orcid":false,"given":"Paul","family":"Koller","sequence":"first","affiliation":[{"name":"Hematology, City of Hope Comprehensive Cancer Center, Duarte, California, 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Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee L","family":"Chin","sequence":"additional","affiliation":[{"name":"Cancer Systems Imaging, The University of Texas Health Science Center at Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4247-2949","authenticated-orcid":false,"given":"Zhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng-Huan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department 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