{"doi":"10.1101/2025.07.02.662848","title":"PDL1 CHECKPOINT BLOCKADE SYNERGIZES WITH NILOTINIB BUT NOT DASATINIB TO PREVENT LEUKEMIA RELAPSE","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":569820,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":960433,"name":"Hrishi Venkatesh","orcid":"0000-0002-2938-3856","position":1,"is_corresponding":false},{"id":1267886,"name":"Enoc Granados Centeno","orcid":"0000-0002-9812-1200","position":2,"is_corresponding":false},{"id":568717,"name":"Lynn Heltemes-Harris","orcid":"0000-0002-2668-8005","position":3,"is_corresponding":false},{"id":1475307,"name":"G. Wilkins Hubbard","orcid":null,"position":4,"is_corresponding":false},{"id":1475308,"name":"Taylor L Maiers","orcid":null,"position":5,"is_corresponding":false},{"id":318062,"name":"Thamotharampillai Dileepan","orcid":"0000-0002-2810-6996","position":6,"is_corresponding":false},{"id":86330,"name":"Sean Tracy","orcid":"0000-0001-7047-2589","position":7,"is_corresponding":false},{"id":374880,"name":"Michael A. Farrar","orcid":"0000-0002-5569-0366","position":8,"is_corresponding":false},{"id":1475306,"name":"Elizabeth C Morgan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:03.510013Z","pmid":"40631161","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}