{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:06:06Z","timestamp":1787785566630,"version":"build-2784847793"},"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Knowledge Foundation","award":["20190010"],"award-info":[{"award-number":["20190010"]}]},{"name":"Stig and Ragna Gorthon"},{"name":"EU Interreg \u00d6KS"},{"name":"Welander Finsen Foundation"},{"name":"Inga and John Hain Foundation"},{"name":"Eva and Ingemar Nilsson Foundation"},{"DOI":"10.13039\/100016409","name":"Gyllenstiernska Krapperup Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016409","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gustaf Th Olsson Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec019\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evade immunosurveillance many cancers convert tryptophan (Trp) into kynurenine (Kyn), which induces immunotolerance and suppresses immune responses. Elevated Kyn amounts have been found in blood from patients with cutaneous melanoma. This study aimed to investigate whether higher Kyn abundance and lower Trp abundance can be detected on the surface of cutaneous melanoma lesions compared with adjacent non-lesional skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec020\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixteen patients with suspected melanomas were enrolled in this study. All lesions were excised and histopathologically diagnosed: 7 lesions were diagnosed as invasive malignant melanomas (MM), 6 as melanomas in situ (MIS), and 3 as benign lesions (BL). Non-invasive metabolite sampling was performed by tape stripping of suspected skin lesions and adjacent healthy non-lesional (NL) skin. Trp, Kyn, tyrosine (Tyr), and phenylalanine (Phe) were quantified by liquid chromatography-tandem mass spectrometry (LC-MS\/MS). Electrical impedance spectroscopy (EIS) measurements were conducted to assess skin barrier integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec021\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Levels of all metabolites, Tyr (x6), Phe (x6), Trp (x5), and Kyn (x3), were significantly higher in MM lesions compared with adjacent NL skin, resulting in an elevated Trp\/Kyn ratio. Trp levels increased less than Phe and Tyr levels, suggesting a potential increase in Trp depletion. Skin resistance in MM lesions was half that of NL skin. No differences were observed between MIS or BL and NL skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec022\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Non-invasive skin sampling revealed elevated Tyr, Phe, Trp and Kyn levels in MM skin, which is likely the result of compromised skin barrier at this stage of cutaneous melanoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0326457","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T13:34:32Z","timestamp":1750772072000},"page":"e0326457","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Non-invasive tape sampling of tryptophan and kynurenine in relation to phenylalanine and tyrosine from melanoma and adjacent non-lesional skin: A pilot study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-0633","authenticated-orcid":true,"given":"Skaidre","family":"Jankovskaja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sp\u00e9gel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7363-0455","authenticated-orcid":true,"given":"Kari","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6254-8539","authenticated-orcid":true,"given":"Sebastian","family":"Bj\u00f6rklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Bost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Engblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5104-2943","authenticated-orcid":true,"given":"Oksana","family":"Rogova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Morin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete","family":"Haedersdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Malmsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris D.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tautgirdas","family":"Ruzgas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"3","key":"pone.0326457.ref001","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"pone.0326457.ref002","author":"World Health Organization (WHO)","year":"2017"},{"issue":"5","key":"pone.0326457.ref003","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamadermatol.2022.0160","article-title":"Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040","volume":"158","author":"M Arnold","year":"2022","journal-title":"JAMA Dermatol"},{"issue":"5","key":"pone.0326457.ref004","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1586\/17469872.3.5.569","article-title":"Current concepts of metastasis in melanoma","volume":"3","author":"B Zbytek","year":"2008","journal-title":"Expert Rev Dermatol"},{"issue":"36","key":"pone.0326457.ref005","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2009.23.4799","article-title":"Final version of 2009 AJCC melanoma staging and classification","volume":"27","author":"CM Balch","year":"2009","journal-title":"J Clin Oncol"},{"key":"pone.0326457.ref006","doi-asserted-by":"crossref","first-page":"642380","DOI":"10.3389\/fmed.2021.642380","article-title":"Molecular Biomarkers for Melanoma Screening, Diagnosis and Prognosis: Current State and Future Prospects","volume":"8","author":"DC Deacon","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"pone.0326457.ref007","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41598-020-79903-w","article-title":"Non-invasive skin sampling of tryptophan\/kynurenine ratio in vitro towards a skin cancer biomarker","volume":"11","author":"S Jankovskaja","year":"2021","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0326457.ref008","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1034\/j.1600-0625.2000.009003165.x","article-title":"The 500 Dalton rule for the skin penetration of chemical compounds and drugs","volume":"9","author":"JD Bos","year":"2000","journal-title":"Exp Dermatol"},{"issue":"6","key":"pone.0326457.ref009","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1046\/j.1523-1747.2003.12606.x","article-title":"The organization of human epidermis: functional epidermal units and phi proportionality","volume":"121","author":"SB Hoath","year":"2003","journal-title":"J Invest Dermatol"},{"issue":"6","key":"pone.0326457.ref010","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1007\/s00726-012-1409-5","article-title":"Protein and non-protein biomarkers in melanoma: a critical update","volume":"43","author":"N Tandler","year":"2012","journal-title":"Amino Acids"},{"issue":"1","key":"pone.0326457.ref011","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000096906","article-title":"Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients","volume":"214","author":"G Weinlich","year":"2007","journal-title":"Dermatology"},{"issue":"1","key":"pone.0326457.ref012","doi-asserted-by":"crossref","first-page":"4346","DOI":"10.1038\/s41467-019-12361-9","article-title":"Metabolomic adaptations and correlates of survival to immune checkpoint blockade","volume":"10","author":"H Li","year":"2019","journal-title":"Nat Commun"},{"key":"pone.0326457.ref013","doi-asserted-by":"crossref","first-page":"736498","DOI":"10.3389\/fimmu.2021.736498","article-title":"Clinical Relevance of Serum Kyn\/Trp Ratio and Basal and IFN\u03b3-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma","volume":"12","author":"A Meireson","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0326457.ref014","first-page":"485","article-title":"Tryptophan-catabolizing enzymes - party of three","volume":"5","author":"HJ Ball","year":"2014","journal-title":"Front Immunol"},{"issue":"8","key":"pone.0326457.ref015","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nbt.4180","article-title":"Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme","volume":"36","author":"TA Triplett","year":"2018","journal-title":"Nat Biotechnol"},{"issue":"1","key":"pone.0326457.ref016","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/s41467-018-04366-7","article-title":"Single cell analysis of kynurenine and System L amino acid transport in T cells","volume":"9","author":"LV Sinclair","year":"2018","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0326457.ref017","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.it.2016.01.002","article-title":"IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance","volume":"37","author":"DH Munn","year":"2016","journal-title":"Trends Immunol"},{"issue":"6","key":"pone.0326457.ref018","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.18632\/oncotarget.6467","article-title":"Understanding the role of the kynurenine pathway in human breast cancer immunobiology","volume":"7","author":"B Heng","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0326457.ref019","first-page":"67","article-title":"The Kynurenine Pathway Is a Double-Edged Sword in Immune-Privileged Sites and in Cancer: Implications for Immunotherapy","volume":"9","author":"J-P Routy","year":"2016","journal-title":"Int J Tryptophan Res"},{"issue":"2","key":"pone.0326457.ref020","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.celrep.2015.08.077","article-title":"Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner","volume":"13","author":"RB Holmgaard","year":"2015","journal-title":"Cell Rep"},{"issue":"10","key":"pone.0326457.ref021","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nm934","article-title":"Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase","volume":"9","author":"C Uyttenhove","year":"2003","journal-title":"Nat Med"},{"issue":"5","key":"pone.0326457.ref022","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/bjd.13100","article-title":"Peritumoral indoleamine 2,3-dioxygenase expression in melanoma: an early marker of resistance to immune control?","volume":"171","author":"I Chevolet","year":"2014","journal-title":"Br J Dermatol"},{"issue":"3","key":"pone.0326457.ref023","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jid.2017.09.036","article-title":"Indoleamine 2,3-Dioxygenase Expression in Primary Cutaneous Melanoma Correlates with Breslow Thickness and Is of Significant Prognostic Value for Progression-Free Survival","volume":"138","author":"F Rubel","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"7","key":"pone.0326457.ref024","doi-asserted-by":"crossref","first-page":"815","DOI":"10.3390\/biom14070815","article-title":"Exploring the Surface: Sampling of Potential Skin Cancer Biomarkers Kynurenine and Tryptophan, Studied on 3D Melanocyte and Melanoma Models","volume":"14","author":"S Hasterok","year":"2024","journal-title":"Biomolecules"},{"issue":"9","key":"pone.0326457.ref025","first-page":"995","article-title":"Shave and punch biopsy for skin lesions","volume":"84","author":"H Pickett","year":"2011","journal-title":"Am Fam Physician"},{"issue":"6","key":"pone.0326457.ref026","doi-asserted-by":"crossref","first-page":"140","DOI":"10.4172\/1948-5956.1000076","article-title":"A case report - Volatile metabolomic signature of malignant melanoma using matching skin as a control","volume":"3","author":"T Abaffy","year":"2011","journal-title":"J Cancer Sci Ther"},{"issue":"6","key":"pone.0326457.ref027","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/pcmr.13182","article-title":"ToF-SIMS imaging reveals changes in tumor cell lipids during metastatic progression of melanoma","volume":"37","author":"N Neittaanm\u00e4ki","year":"2024","journal-title":"Pigment Cell Melanoma Res"},{"issue":"1","key":"pone.0326457.ref028","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3390\/pharmaceutics14010079","article-title":"Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers","volume":"14","author":"M Morin","year":"2021","journal-title":"Pharmaceutics"},{"issue":"14","key":"pone.0326457.ref029","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/rcm.3601","article-title":"Determination of 13C\/12C ratios of endogenous urinary steroids: method validation, reference population and application to doping control purposes","volume":"22","author":"T Piper","year":"2008","journal-title":"Rapid Commun Mass Spectrom"},{"issue":"2","key":"pone.0326457.ref030","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3390\/pharmaceutics14020313","article-title":"Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers-An Explorative In Vivo Study","volume":"14","author":"M Morin","year":"2022","journal-title":"Pharmaceutics"},{"issue":"15","key":"pone.0326457.ref031","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1021\/acs.analchem.1c05470","article-title":"Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers","volume":"94","author":"S Jankovskaja","year":"2022","journal-title":"Anal Chem"},{"issue":"1","key":"pone.0326457.ref032","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/2303-9027.127122","article-title":"How good is fine needle aspiration? What results should you expect?","volume":"3","author":"P Eisendrath","year":"2014","journal-title":"Endosc Ultrasound"},{"issue":"1","key":"pone.0326457.ref033","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1245\/s10434-006-9341-0","article-title":"Diagnostic accuracy of fine needle biopsy for metastatic melanoma and its implications for patient management","volume":"15","author":"A Doubrovsky","year":"2008","journal-title":"Ann Surg Oncol"},{"issue":"1","key":"pone.0326457.ref034","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/cncy.22488","article-title":"Cytologic diagnosis of metastatic melanoma by FNA: A practical review","volume":"130","author":"A Ronchi","year":"2022","journal-title":"Cancer Cytopathol"},{"key":"pone.0326457.ref035","doi-asserted-by":"crossref","first-page":"30075","DOI":"10.1038\/srep30075","article-title":"Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer","volume":"6","author":"I Ryoo","year":"2016","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0326457.ref036","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaad.2016.07.038","article-title":"Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma","volume":"76","author":"P Gerami","year":"2017","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"pone.0326457.ref037","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/CMR.0000000000000478","article-title":"Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions","volume":"28","author":"LK Ferris","year":"2018","journal-title":"Melanoma Res"},{"issue":"3","key":"pone.0326457.ref038","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jaad.2023.05.030","article-title":"RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma: A diagnostic study","volume":"89","author":"IM Heerfordt","year":"2023","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"pone.0326457.ref039","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1093\/jalm\/jfaa009","article-title":"Temporal Correlations of Skin and Blood Metabolites with Clinical Outcomes of Biologic Therapy in Psoriasis","volume":"5","author":"EP Dutkiewicz","year":"2020","journal-title":"J Appl Lab Med"},{"issue":"5","key":"pone.0326457.ref040","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1021\/jacsau.0c00074","article-title":"Rapid Noninvasive Skin Monitoring by Surface Mass Recording and Data Learning","volume":"1","author":"Y Zhu","year":"2021","journal-title":"JACS Au"},{"issue":"2","key":"pone.0326457.ref041","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2022-069694","article-title":"BioMEL: a translational research biobank of melanocytic lesions and melanoma","volume":"14","author":"T Helkkula","year":"2024","journal-title":"BMJ Open"},{"issue":"10","key":"pone.0326457.ref042","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1111\/all.14842","article-title":"Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis","volume":"76","author":"AO Rinaldi","year":"2021","journal-title":"Allergy"},{"issue":"1","key":"pone.0326457.ref043","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/all.15895","article-title":"Electrical impedance spectroscopy detects skin barrier dysfunction in childhood atopic dermatitis","volume":"79","author":"M Sasaki","year":"2024","journal-title":"Allergy"},{"issue":"3","key":"pone.0326457.ref044","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1034\/j.1600-0846.2003.00017.x","article-title":"Assessment of skin lesions and skin cancer using simple electrical impedance indices","volume":"9","author":"P Aberg","year":"2003","journal-title":"Skin Res Technol"},{"issue":"12","key":"pone.0326457.ref045","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1016\/j.bpj.2013.05.008","article-title":"Skin membrane electrical impedance properties under the influence of a varying water gradient","volume":"104","author":"S Bj\u00f6rklund","year":"2013","journal-title":"Biophys J"},{"issue":"1","key":"pone.0326457.ref046","doi-asserted-by":"crossref","first-page":"17218","DOI":"10.1038\/s41598-020-73684-y","article-title":"Skin hydration dynamics investigated by electrical impedance techniques in vivo and in vitro","volume":"10","author":"M Morin","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0326457.ref047","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"00","author":"JE Gershenwald","year":"2017","journal-title":"CA Cancer J Clin"},{"key":"pone.0326457.ref048","article-title":"Malignant melanoma of skin","volume-title":"TNM classification of malignant tumours","author":"JD Brierley","year":"2017"},{"key":"pone.0326457.ref049","author":"Regionala Cancercentrum"},{"issue":"3","key":"pone.0326457.ref050","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.it.2012.10.001","article-title":"Indoleamine 2,3 dioxygenase and metabolic control of immune responses","volume":"34","author":"DH Munn","year":"2013","journal-title":"Trends Immunol"},{"issue":"11","key":"pone.0326457.ref051","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1001\/archderm.144.11.1468","article-title":"Factors associated with the number of lesions excised for each skin cancer: a study of primary care physicians in Queensland, Australia","volume":"144","author":"PD Baade","year":"2008","journal-title":"Arch Dermatol"},{"issue":"5","key":"pone.0326457.ref052","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/1523-1747.ep12398620","article-title":"Stratum corneum moisturization at the molecular level","volume":"103","author":"AV Rawlings","year":"1994","journal-title":"J Invest Dermatol"},{"issue":"3","key":"pone.0326457.ref053","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1365-2133.2010.09805.x","article-title":"Extraction and quantification of amino acids in human stratum corneum in vivo","volume":"163","author":"J-P Sylvestre","year":"2010","journal-title":"Br J Dermatol"},{"key":"pone.0326457.ref054","doi-asserted-by":"crossref","first-page":"122891","DOI":"10.1016\/j.ijpharm.2023.122891","article-title":"Effects of storage conditions on permeability and electrical impedance properties of the skin barrier","volume":"637","author":"M Morin","year":"2023","journal-title":"Int J Pharm"},{"issue":"2","key":"pone.0326457.ref055","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jconrel.2005.10.012","article-title":"Relationships between skin\u2019s electrical impedance and permeability in the presence of chemical enhancers","volume":"110","author":"P Karande","year":"2006","journal-title":"J Control Release"},{"issue":"2","key":"pone.0326457.ref056","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jconrel.2010.01.005","article-title":"A water gradient can be used to regulate drug transport across skin","volume":"143","author":"S Bj\u00f6rklund","year":"2010","journal-title":"J Control Release"},{"issue":"1","key":"pone.0326457.ref057","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1055-9965.EPI-14-0980","article-title":"Tyrosine, phenylalanine, and tryptophan in gastroesophageal malignancy: a systematic review","volume":"24","author":"T Wiggins","year":"2015","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"11","key":"pone.0326457.ref058","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1158\/0008-5472.CAN-08-4806","article-title":"Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry","volume":"69","author":"A Hirayama","year":"2009","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0326457.ref059","doi-asserted-by":"crossref","first-page":"8864","DOI":"10.1038\/s41598-017-08433-9","article-title":"Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling","volume":"7","author":"H-Y Kim","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0326457.ref060","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.clinms.2018.08.001","article-title":"Comparative metabolite profiling of a metastatic and primary melanoma cell line using untargeted metabolomics: A case study","volume":"10","author":"Z Yu","year":"2018","journal-title":"Clin Mass Spectrom"},{"issue":"2","key":"pone.0326457.ref061","article-title":"The Skin Microbiome: A New Key Player in Melanoma, From Onset to Metastatic Stage","volume":"38","author":"J-M L\u2019Orphelin","year":"2025","journal-title":"Pigment Cell Melanoma Res"},{"issue":"11","key":"pone.0326457.ref062","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1023\/A:1016280714593","article-title":"Apparent pKa of the fatty acids within ordered mixtures of model human stratum corneum lipids","volume":"12","author":"R Lieckfeldt","year":"1995","journal-title":"Pharm Res"},{"issue":"2","key":"pone.0326457.ref063","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0378-5173(91)90053-Q","article-title":"Transdermal permeability and skin accumulation of amino acids","volume":"72","author":"A Ruland","year":"1991","journal-title":"International Journal of Pharmaceutics"},{"issue":"1","key":"pone.0326457.ref064","doi-asserted-by":"crossref","DOI":"10.1016\/j.chembiol.2024.12.007","article-title":"Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome","volume":"32","author":"A Uberoi","year":"2025","journal-title":"Cell Chem Biol"},{"issue":"6","key":"pone.0326457.ref065","article-title":"A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor","volume":"143","author":"J Yu","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"7","key":"pone.0326457.ref066","doi-asserted-by":"crossref","DOI":"10.1016\/j.jid.2021.12.003","article-title":"An Epidemiologic Analysis of Melanoma Overdiagnosis in the United States, 1975-2017","volume":"142","author":"NR Kurtansky","year":"2022","journal-title":"J Invest Dermatol"},{"key":"pone.0326457.ref067","doi-asserted-by":"crossref","first-page":"636081","DOI":"10.3389\/fimmu.2021.636081","article-title":"Tryptophan: A Rheostat of Cancer Immune Escape Mediated by Immunosuppressive Enzymes IDO1 and TDO","volume":"12","author":"M Kim","year":"2021","journal-title":"Front Immunol"},{"issue":"6","key":"pone.0326457.ref068","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 Immunol"},{"key":"pone.0326457.ref069","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fonc.2020.00051","article-title":"Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma","volume":"10","author":"S Rad Pour","year":"2020","journal-title":"Front Oncol"},{"key":"pone.0326457.ref070","doi-asserted-by":"crossref","first-page":"105056","DOI":"10.1016\/j.ebiom.2024.105056","article-title":"Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases","volume":"102","author":"DMM Harris","year":"2024","journal-title":"EBioMedicine"},{"issue":"1","key":"pone.0326457.ref071","doi-asserted-by":"crossref","first-page":"2170095","DOI":"10.1080\/2162402X.2023.2170095","article-title":"The signaling function of IDO1 incites the malignant progression of mouse B16 melanoma","volume":"12","author":"E Orecchini","year":"2023","journal-title":"Oncoimmunology"},{"key":"pone.0326457.ref072","doi-asserted-by":"crossref","first-page":"1134551","DOI":"10.3389\/fimmu.2023.1134551","article-title":"The catalytic inhibitor epacadostat can affect the non-enzymatic function of IDO1","volume":"14","author":"E Panfili","year":"2023","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0326457.ref073","doi-asserted-by":"crossref","first-page":"2204753","DOI":"10.1080\/2162402X.2023.2204753","article-title":"Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III\/IV melanoma","volume":"12","author":"JD Oldan","year":"2023","journal-title":"Oncoimmunology"},{"issue":"8","key":"pone.0326457.ref074","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1470-2045(19)30274-8","article-title":"Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301\/KEYNOTE-252): a phase 3, randomised, double-blind study","volume":"20","author":"GV Long","year":"2019","journal-title":"Lancet Oncol"},{"key":"pone.0326457.ref075","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1186\/s12885-023-10971-7","article-title":"A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679\/ECHO-302)","volume":"23","author":"PN Jr Lara","year":"2024","journal-title":"BMC Cancer"},{"key":"pone.0326457.ref076","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1186\/s12885-023-11213-6","article-title":"Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303\/KEYNOTE-698 study","volume":"23","author":"I Cicin","year":"2024","journal-title":"BMC Cancer"},{"issue":"15","key":"pone.0326457.ref077","doi-asserted-by":"crossref","first-page":"18490","DOI":"10.1021\/acsami.4c00513","article-title":"Metabolic Modulation of Kynurenine Based on Kynureninase-Loaded Nanoparticle Depot Overcomes Tumor Immune Evasion in Cancer Immunotherapy","volume":"16","author":"S-Y Chae","year":"2024","journal-title":"ACS Appl Mater Interfaces"},{"issue":"11","key":"pone.0326457.ref078","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-007495","article-title":"Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy","volume":"11","author":"C Kober","year":"2023","journal-title":"J Immunother Cancer"},{"key":"pone.0326457.ref079","doi-asserted-by":"crossref","first-page":"103734","DOI":"10.1016\/j.ebiom.2021.103734","article-title":"Kynurenine induces T cell fat catabolism and has limited suppressive effects in vivo","volume":"74","author":"PJ Siska","year":"2021","journal-title":"EBioMedicine"},{"issue":"1","key":"pone.0326457.ref080","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1038\/s41467-021-24785-3","article-title":"3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine","volume":"12","author":"CC Clement","year":"2021","journal-title":"Nat Commun"},{"issue":"9","key":"pone.0326457.ref081","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1007\/s13555-024-01248-3","article-title":"Prospective Clinical Study: Full-Body Blue Irradiation in the Treatment of Atopic Dermatitis","volume":"14","author":"M Sadowska","year":"2024","journal-title":"Dermatol Ther (Heidelb)"},{"issue":"4","key":"pone.0326457.ref082","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1159\/000450789","article-title":"Activation of Tryptophan and Phenylalanine Catabolism in the Remission Phase of Allergic Contact Dermatitis: A Pilot Study","volume":"170","author":"A Zinkevi\u010dien\u0117","year":"2016","journal-title":"Int Arch Allergy Immunol"},{"issue":"6","key":"pone.0326457.ref083","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.nut.2014.12.023","article-title":"Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis","volume":"31","author":"AL Maltos","year":"2015","journal-title":"Nutrition"},{"issue":"2","key":"pone.0326457.ref084","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jdermsci.2022.07.006","article-title":"Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa","volume":"107","author":"Y-F Chen","year":"2022","journal-title":"J Dermatol Sci"},{"issue":"20","key":"pone.0326457.ref085","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.140598","article-title":"Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa","volume":"5","author":"L Guenin-Mac\u00e9","year":"2020","journal-title":"JCI Insight"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0326457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T13:34:54Z","timestamp":1750772094000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0326457"}},"subtitle":[],"editor":[{"given":"Krishnendu","family":"Sinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":85,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0326457","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]}}}