{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:58:56Z","timestamp":1781287136588,"version":"3.54.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung adenocarcinoma (LUAD) is a predominant subtype of lung cancer associated with an unfavorable prognosis. However, the roles of the tumor microenvironment (TME) and Kynureninase (KYNU) in LUAD remain largely unclear. This study aimed to investigate the potential role of KYNU in macrophages and LUAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All LUAD related data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression of KYNU was analyzed across different cell types following dimensionality reduction analysis. Immune cell infiltration and immunotherapy response prediction were performed using CIBERSORT and TIMER, respectively. Gene set variation analysis (GSVA) was employed for functional enrichment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among all immune cells in LUAD, KYNU was primarily expressed in monocytes and macrophages. The upregulated genes in KYNU+macrophages group were significantly enriched in in gene ontology (GO) terms related to antigen processing and presentation. There were increased MHC-I\/ MHC-II signal interactions between KYNU+macrophages and B cells as well as T cells. In LUAD patients with higher proportions of KYNU+macrophages, a significantly greater number of patients benefited from immunotherapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033). GSVA results indicated that the MHC pathway was significantly activated in high KYNU+macrophage group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>KYNU is primarily in LUAD macrophages, contributing to the distinct immune features and correlating with the enhanced antigen presentation in LUAD. This study preliminarily confirms that KYNU may serve as a potential biomarker for immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351622","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:37:18Z","timestamp":1781285838000},"page":"e0351622","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["KYNU in macrophages contributes to the unique immune feature of LUAD via integrating single-cell and bulk RNA sequencing data: an exploratory 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secretion to promote lung adenocarcinoma metastasis via Hippo pathway","volume":"11","author":"J Chen","year":"2021","journal-title":"Clin Transl Med"},{"issue":"1","key":"pone.0351622.ref003","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/s12967-022-03723-x","article-title":"Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer","volume":"20","author":"J Pang","year":"2022","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0351622.ref004","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1038\/s41467-020-16164-1","article-title":"Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma","volume":"11","author":"N Kim","year":"2020","journal-title":"Nat Commun"},{"issue":"7948","key":"pone.0351622.ref005","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41586-022-05672-3","article-title":"Single-cell spatial landscapes of the lung tumour immune microenvironment","volume":"614","author":"M Sorin","year":"2023","journal-title":"Nature"},{"issue":"8","key":"pone.0351622.ref006","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.mayocp.2019.01.013","article-title":"Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment","volume":"94","author":"N Duma","year":"2019","journal-title":"Mayo Clin Proc"},{"issue":"5","key":"pone.0351622.ref007","doi-asserted-by":"crossref","first-page":"786","DOI":"10.21037\/tlcr-22-318","article-title":"Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance","volume":"11","author":"C Zhang","year":"2022","journal-title":"Transl Lung Cancer Res"},{"issue":"10299","key":"pone.0351622.ref008","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"AA Thai","year":"2021","journal-title":"Lancet"},{"issue":"15","key":"pone.0351622.ref009","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1158\/1078-0432.CCR-18-1538","article-title":"Immunotherapy in non-small cell lung cancer: facts and hopes","volume":"25","author":"DB Doroshow","year":"2019","journal-title":"Clinical Cancer Research"},{"issue":"10","key":"pone.0351622.ref010","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1002\/cam4.2327","article-title":"Crosstalk between cancer and immune cells: Role of tumor-associated macrophages in the tumor microenvironment","volume":"8","author":"J Wang","year":"2019","journal-title":"Cancer Med"},{"issue":"13","key":"pone.0351622.ref011","doi-asserted-by":"crossref","first-page":"6995","DOI":"10.3390\/ijms22136995","article-title":"Macrophage polarization states in the tumor microenvironment","volume":"22","author":"AJ Boutilier","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0351622.ref012","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.lungcan.2018.07.015","article-title":"The intratumoral distribution influences the prognostic impact of CD68- and CD204-positive macrophages in non-small cell lung cancer","volume":"123","author":"Z Li","year":"2018","journal-title":"Lung Cancer"},{"issue":"1","key":"pone.0351622.ref013","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s13046-018-0878-0","article-title":"Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling","volume":"37","author":"F Xu","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"pone.0351622.ref014","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.abb.2013.10.020","article-title":"Structure and mechanism of kynureninase","volume":"544","author":"RS Phillips","year":"2014","journal-title":"Archives of Biochemistry and 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PI3K\/AKT pathway","volume":"45","author":"C Ci","year":"2020","journal-title":"Clin Exp Dermatol"},{"issue":"12","key":"pone.0351622.ref018","doi-asserted-by":"crossref","first-page":"5826","DOI":"10.7150\/thno.108817","article-title":"GPX4 knockdown suppresses M2 macrophage polarization in gastric cancer by modulating kynurenine metabolism","volume":"15","author":"J Xu","year":"2025","journal-title":"Theranostics"},{"issue":"1","key":"pone.0351622.ref019","doi-asserted-by":"crossref","first-page":"2055703","DOI":"10.1080\/2162402X.2022.2055703","article-title":"Superior antitumor immunotherapy efficacy of kynureninase modified CAR-T cells through targeting kynurenine metabolism","volume":"11","author":"Q Yang","year":"2022","journal-title":"Oncoimmunology"},{"issue":"2","key":"pone.0351622.ref020","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"D Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"pone.0351622.ref021","article-title":"Dimensionality reduction for visualizing single-cell data using UMAP","author":"E Becht","year":"2018","journal-title":"Nature Biotechnology"},{"issue":"1","key":"pone.0351622.ref022","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"S Jin","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0351622.ref023","doi-asserted-by":"crossref","first-page":"1055122","DOI":"10.3389\/fonc.2023.1055122","article-title":"MMP11 is associated with the immune response and immune microenvironment in EGFR-mutant lung adenocarcinoma","volume":"13","author":"L Bai","year":"2023","journal-title":"Front Oncol"},{"issue":"6","key":"pone.0351622.ref024","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1056\/NEJMoa1616361","article-title":"NAD deficiency, congenital malformations, and niacin supplementation","volume":"377","author":"H Shi","year":"2017","journal-title":"The New England Journal of Medicine"},{"issue":"5","key":"pone.0351622.ref025","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1111\/jcmm.16296","article-title":"KYNU, a novel potential target that underpins CD44-promoted breast tumour cell invasion","volume":"25","author":"M Al-Mansoob","year":"2021","journal-title":"J Cell Mol Med"},{"key":"pone.0351622.ref026","doi-asserted-by":"crossref","first-page":"145736","DOI":"10.1016\/j.gene.2021.145736","article-title":"TDO2 knockdown inhibits colorectal cancer progression via TDO2-KYNU-AhR pathway","volume":"792","author":"L Zhao","year":"2021","journal-title":"Gene"},{"issue":"4","key":"pone.0351622.ref027","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1158\/2159-8290.CD-20-1808","article-title":"Therapeutic targeting of the tumor microenvironment","volume":"11","author":"L Bejarano","year":"2021","journal-title":"Cancer Discov"},{"issue":"5","key":"pone.0351622.ref028","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41568-021-00339-z","article-title":"Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion","volume":"21","author":"S Jhunjhunwala","year":"2021","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"pone.0351622.ref029","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.jaci.2015.09.055","article-title":"The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases","volume":"137","author":"JL Harden","year":"2016","journal-title":"J Allergy Clin 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