{"doi":"10.1016/j.jtho.2022.11.008","title":"An Interleukin-15 Superagonist Enables Antitumor Efficacy of Natural Killer Cells Against All Molecular Variants of SCLC","abstract":"INTRODUCTION: SCLC is a highly aggressive tumor with a 5-year survival rate of less than 6%. A heterogeneous disease, SCLC is classified into four subtypes that include tumors with neuroendocrine and non-neuroendocrine features. Immune checkpoint blockade has been recently added for the frontline treatment of SCLC; however, this therapy has only led to modest clinical improvements. The lack of clinical benefit in a cancer type known to have a high tumor mutational burden has been attributed to poor T-cell infiltration and low expression of MHC-class I in most SCLC tumors. In an attempt to devise a more effective immunotherapeutic regimen, this study investigated an alternate approach on the basis of the use of the clinical-stage interleukin-15 superagonist, N-803. METHODS: Preclinical models of SCLC spanning all molecular subtypes were used to evaluate the susceptibility of SCLC to natural killer (NK)-mediated lysis in vitro, including NK cells activated by N-803. Antitumor activity of N-803 was evaluated in vivo with a xenograft model of SCLC. RESULTS: In vitro and in vivo data revealed differences in susceptibility of SCLC subtypes to lysis by NK cells and that NK cells activated by N-803 effectively lyse SCLC tumor cells across all variant subtypes, regardless of their expression of MHC-class I. CONCLUSIONS: These findings highlight the potential of a novel immune-based intervention using a cytokine-based therapeutic option for the treatment of SCLC. We hypothesize that N-803 may provide benefit to most patients with SCLC, including those with immunologically cold tumors lacking MHC expression.","journal":"Journal of Thoracic Oncology","year":2022,"id":252191,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":234208,"name":"Lucas A. Horn","orcid":null,"position":1,"is_corresponding":false},{"id":831899,"name":"Haiyan Qin","orcid":"0000-0003-3731-5236","position":2,"is_corresponding":false},{"id":832448,"name":"Madeline Dahut","orcid":null,"position":3,"is_corresponding":false},{"id":847888,"name":"Masafumi Iida","orcid":"0000-0003-0095-9767","position":4,"is_corresponding":false},{"id":896652,"name":"Dan Yacubovich","orcid":null,"position":5,"is_corresponding":false},{"id":284009,"name":"Duane H. Hamilton","orcid":"0000-0002-9730-8209","position":6,"is_corresponding":false},{"id":253875,"name":"Anish Thomas","orcid":"0000-0003-3293-3115","position":7,"is_corresponding":false},{"id":239943,"name":"Jeffrey Schlom","orcid":"0000-0001-7932-4072","position":8,"is_corresponding":false},{"id":231605,"name":"Claudia Palena","orcid":"0000-0002-0445-4486","position":9,"is_corresponding":false},{"id":231604,"name":"Kristen Fousek","orcid":"0000-0002-2307-5000","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36410696","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":[]}