{"doi":"10.26508/lsa.202301999","title":"APR-246 increases tumor antigenicity independent of p53","abstract":"We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate that APR-246 and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity of tumor cells directly. MQ treatment of murine B16F10 melanoma cells promoted activation of melanoma-specific CD8 + T cells and increased the efficacy of a tumor cell vaccine using MQ-treated cells even when the B16F10 cells lacked p53. We then designed a novel combination of APR-246 with the TLR-4 agonist, monophosphoryl lipid A, and a CD40 agonist to further enhance these immunogenic effects and demonstrated a significant antitumor response. We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor’s p53 mutation status.","journal":"Life Science Alliance","year":2023,"id":373698,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":726985,"name":"Divya Venkatesh","orcid":"0000-0003-4787-973X","position":1,"is_corresponding":false},{"id":229695,"name":"Cailian Liu","orcid":null,"position":2,"is_corresponding":false},{"id":227528,"name":"Sadna Budhu","orcid":"0000-0002-3284-1408","position":3,"is_corresponding":false},{"id":617706,"name":"Hong Zhong","orcid":"0000-0002-9931-7504","position":4,"is_corresponding":false},{"id":477278,"name":"Mariam M. George","orcid":"0000-0003-3166-6844","position":5,"is_corresponding":false},{"id":1134982,"name":"Daniel Thach","orcid":"0000-0002-7609-8775","position":6,"is_corresponding":false},{"id":1134983,"name":"Zhong‐Ke Yao","orcid":"0000-0002-0427-686X","position":7,"is_corresponding":false},{"id":335056,"name":"Ouathek Ouerfelli","orcid":"0000-0002-7038-0219","position":8,"is_corresponding":false},{"id":555718,"name":"Hengrui Liu","orcid":"0000-0002-5214-1572","position":9,"is_corresponding":false},{"id":90272,"name":"Brent R. Stockwell","orcid":"0000-0002-3532-3868","position":10,"is_corresponding":false},{"id":229692,"name":"Luís Felipe Campesato","orcid":null,"position":11,"is_corresponding":false},{"id":227533,"name":"Dmitriy Zamarin","orcid":"0000-0002-0094-0161","position":12,"is_corresponding":false},{"id":109845,"name":"Roberta Zappasodi","orcid":"0000-0002-7031-6671","position":13,"is_corresponding":false},{"id":3666,"name":"Jedd D. Wolchok","orcid":"0000-0001-6718-2222","position":14,"is_corresponding":false},{"id":109855,"name":"Taha Merghoub","orcid":"0000-0002-1518-5111","position":15,"is_corresponding":false},{"id":890206,"name":"Judith Michels","orcid":"0000-0002-9640-0222","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:16:07.080027Z","pmid":"37891002","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":[]}