{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:51:11Z","timestamp":1768524671385,"version":"3.49.0"},"posted":{"date-parts":[[2025,7,5]]},"group-title":"Immunology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIAID","award":["R01 AI124512"],"award-info":[{"award-number":["R01 AI124512"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,5]]},"abstract":"<jats:p>Dasatinib and nilotinib are front line Tyrosine Kinase Inhibitors (TKIs) used to treat BCR-ABL+ B cell acute lymphoblastic leukemia (B-ALL) and BCR-ABL+ chronic myelogenous leukemia. We previously showed that combining nilotinib with anti-PD-L1 blockade significantly reduced leukemia relapse. The TKI dasatinib is more commonly used to treat to B-ALL. However, unlike nilotinib, dasatinib also inhibits SRC-family kinases, which may make it less efficacious in combination with anti-PDL1 blockade. Herein we assess the impact of nilotinib versus dasatinib on anti-leukemia immune responses. Dasatinib, but not nilotinib, inhibited T cell proliferation at high doses in-vitro, but neither TKI significantly impacted T cell function or expansion in response to immunization in-vivo with a model antigen (2W1S) plus polyIC-adjuvant. Dasatinib and nilotinib both reduced leukemic blasts equivalently after 5 days of treatment. In contrast, nilotinib and PD-L1 blockade, but not dasatinib plus anti-PDL1, prevented relapse several weeks later. Thus, dasatinib negatively impacts protective anti-leukemia T cell responses that prevent leukemia relapse.<\/jats:p>","DOI":"10.1101\/2025.07.02.662848","type":"posted-content","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T22:50:12Z","timestamp":1751755812000},"source":"Crossref","is-referenced-by-count":0,"title":["PDL1 CHECKPOINT BLOCKADE SYNERGIZES WITH NILOTINIB BUT NOT DASATINIB TO PREVENT LEUKEMIA RELAPSE"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2464-7517","authenticated-orcid":false,"given":"Elizabeth C","family":"Morgan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2938-3856","authenticated-orcid":false,"given":"Hrishi","family":"Venkatesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-1200","authenticated-orcid":false,"given":"Enoc Granados","family":"Centenos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-8005","authenticated-orcid":false,"given":"Lynn M","family":"Heltemes-Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2417-1576","authenticated-orcid":false,"given":"Gregory","family":"Hubbard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor L","family":"Maiers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-6996","authenticated-orcid":false,"given":"Thamotharampillai","family":"Dileepan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean I","family":"Tracy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-0366","authenticated-orcid":false,"given":"Michael A","family":"Farrar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.02.662848","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:04:30Z","timestamp":1768467870000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.02.662848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.07.02.662848","relation":{},"subject":[],"published":{"date-parts":[[2025,7,5]]},"subtype":"preprint"}}