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Despite recent therapeutic advances, including immune checkpoint inhibitors and small\u2010molecule kinase inhibitors, patients frequently develop treatment resistance. Novel models are needed to devise strategies that overcome resistance and further reduce melanoma\u2010related mortality. Interspecies hybrid fish from the\n                    <jats:italic>Xiphophorus<\/jats:italic>\n                    lineage develop mutant\n                    <jats:italic>Epidermal Growth Factor Receptor<\/jats:italic>\n                    (EGFR)\u2010driven melanomas that display morphology, bulk gene expression, disease initiation, and progression processes mimicking those of human melanomas. These similarities have enabled their comparative use in evaluating why human melanomas exhibit cancer cell plasticity and how the cancer cells interact with diverse immune populations. However, it remains unclear whether\n                    <jats:italic>Xiphophorus<\/jats:italic>\n                    melanomas recapitulate some or all these features. To address this, we performed single\u2010nucleus RNA sequencing (snRNAseq) analysis of\n                    <jats:italic>Xiphophorus<\/jats:italic>\n                    melanomas. Employing comparative analyses with results from human melanoma studies, we demonstrate that\n                    <jats:italic>Xiphophorus<\/jats:italic>\n                    melanomas faithfully mimic the cellular heterogeneity observed in human melanoma, including cancer cells, endothelial cells, cancer\u2010associated fibroblasts, B cells, M1 and M2 macrophages, N1 and N2 neutrophils, various T helper cells, and less cytotoxic, but not exhausted CD8+ T cells. Immune and cancer cell subtyping showed\n                    <jats:italic>Xiphophorus<\/jats:italic>\n                    melanoma represented an immune\u2010evaded status.\n                  <\/jats:p>","DOI":"10.1111\/pcmr.70106","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T06:14:11Z","timestamp":1783145651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Human Melanoma Single Cell Profiles to Evolutionary Medicine Model\n                    <i>Xiphophorus<\/i>\n                    Provides Insights in Disease Control"],"prefix":"10.1111","volume":"39","author":[{"given":"Yuan","family":"Lu","sequence":"first","affiliation":[{"name":"Institute for Molecular Life Sciences Texas State University  San Marcos Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Boswell","sequence":"additional","affiliation":[{"name":"Institute for Molecular Life Sciences Texas State University  San Marcos Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Carroll","sequence":"additional","affiliation":[{"name":"Divsion of Animal Sceinces, Department of Surgery, Bond Life Science Center University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggs","family":"X","sequence":"additional","affiliation":[{"name":"School of Natural Sciences Macquarie University  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5997-0001","authenticated-orcid":false,"given":"Yanting","family":"Xing","sequence":"additional","affiliation":[{"name":"Institute for Molecular Life Sciences Texas State University  San Marcos Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley C.","family":"Warren","sequence":"additional","affiliation":[{"name":"Divsion of Animal Sceinces, Department of Surgery, Bond Life Science Center University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Schartl","sequence":"additional","affiliation":[{"name":"Institute for Molecular Life Sciences Texas State University  San Marcos Texas USA"},{"name":"Institute for Pathology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Research Department for Limnology University of Innsbruck  Mondsee Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2017.8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.3377"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","unstructured":"Beatty G. L. E. G.Chiorean M. P.Fishman et\u00a0al.2011. \u201cCD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans. Science.\u201d331 no.6024:1612\u20131616.https:\/\/doi.org\/10.1126\/science.1198443.","DOI":"10.1126\/science.1198443"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104276"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101472"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010021\u201001273\u20109"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107628"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.36.20210163"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.06.014"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2019.11.008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkae298"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12248"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13988"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20101507"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067801"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021601"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010024\u201003220\u20109"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.756001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.006"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021246\u20109"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199807)22:3<210::AID-GCC6>3.0.CO;2-Z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2020.5088"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010020\u20100273\u2010y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188440"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12686"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201036656\u2010x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010133117"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.09.021"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds257"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","unstructured":"Mariathasan S. S. J.Turley D.Nickles et\u00a0al.2018. \u201cTGFbeta Attenuates Tumour Response to PD\u2010L1 Blockade by Contributing to Exclusion of T Cells. 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