{"doi":"10.1101/2024.01.26.577405","title":"Impact of IL-21 on Natural Killer cell proliferation and function – a mathematical and functional assessment","abstract":"Natural killer (NK) cells are currently in use as immunotherapeutic agents for cancer. Many different cytokines are used to generate NK cells including IL-2, IL-12, IL-15 and IL-18 in solution and membrane bound IL-21. These cytokines drive NK cell activation through the integration of STAT and NF-κB pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy between STAT3 and NF-κB transcription factors. Use of IL-21 in solution in the priming, but not post-priming phase of NK cell culture resulted in optimal NK cell proliferation, without compromising cytotoxicity or IFN-γ secretion against hepatocellular carcinoma cell lines. Our work provides a mathematical framework for interrogating NK cell activation for cancer immunotherapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":487806,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1332057,"name":"Indrani Nayak","orcid":"0000-0002-4257-8965","position":1,"is_corresponding":false},{"id":1332454,"name":"Nina Möker","orcid":null,"position":2,"is_corresponding":false},{"id":1332058,"name":"Congcong Zhang","orcid":"0000-0001-9995-3079","position":3,"is_corresponding":false},{"id":431798,"name":"William C. Stewart","orcid":"0000-0002-6153-6613","position":4,"is_corresponding":false},{"id":488177,"name":"Salim I. Khakoo","orcid":"0000-0002-4057-9091","position":5,"is_corresponding":false},{"id":816508,"name":"Jayajit Das","orcid":"0000-0001-9649-4698","position":6,"is_corresponding":false},{"id":1332453,"name":"Rosalba Biondo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:08:10.215754Z","pmid":"38352361","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":[]}