{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:03:22Z","timestamp":1779696202340,"version":"3.53.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), cutaneous melanoma (CM) and acral melanoma (AM), exhibit profound heterogeneity in clinical behaviour and therapeutic response. However, how tumour\u2010immune ecosystems are remodelled across skin cancer types and disease stages, and how these changes influence immune escape and treatment resistance, remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we integrate single\u2010cell transcriptomics data from 102 skin cancer samples (including adjacent normal skin, early\u2010stage and advanced\u2010stage tumours), with bulk RNA\u2010seq prognosis cohorts, immunofluorescence staining and in vitro assays to define clinically relevant immune remodelling patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analyses identify a malignant\n                      <jats:italic>\n                        NARS2\n                        <jats:sup>+<\/jats:sup>\n                        NDUFC2\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      melanoma cell subpopulation, characterised by reduced MHC\u2010I expression, enriched in advanced\u2010stage tumours and associated with worse survival and immunotherapy response. CRISPR screening further showed that\n                      <jats:italic>NARS2<\/jats:italic>\n                      and\n                      <jats:italic>NDUFC2<\/jats:italic>\n                      are necessary for the proliferation of melanoma cells, highlighting these genes as potential therapeutic targets. Tumour\u2010associated macrophages (TAMs) originate from both\n                      <jats:italic>FCN1<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      monocytes and\n                      <jats:italic>\n                        FOLR2\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      tissue\u2010resident macrophages, displaying two polarisation states with distinct prognostic associations. Specifically, pro\u2010inflammatory\n                      <jats:italic>\n                        CXCL9\n                        <jats:sup>+<\/jats:sup>\n                        CXCL10\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      TAMs are enriched in SCC, while tissue\u2010remodelling\n                      <jats:italic>SPP1<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      TAMs are predominant in melanoma. Immunofluorescence staining confirmed that\n                      <jats:italic>SPP1<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      macrophage accumulation correlates with advanced stage, metastasis and poor prognosis in the melanoma cohort. Immune ecotype analysis reveals a transition from \u2018T\u2010cell\u2010dominant\u2019 ecotypes to \u2018desert\u2019 ecotypes as disease advances in BCC, CM and AM. Cell\u2012cell communication analysis shows that \u2018T\u2010cell\u2010dominant\u2019 ecotypes have higher MHC\u2010I signalling pathways in tumour cells, whereas \u2018Desert\u2019 ecotypes have higher\n                      <jats:italic>\n                        SPP1\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      macrophage signalling, underlining the role of\n                      <jats:italic>SPP1<\/jats:italic>\n                      on immune remodelling. Functional assays confirm that melanoma cells could drive M2 polarisation and SPP1 upregulation in macrophages. Knocking down or overexpressing\n                      <jats:italic>SPP1<\/jats:italic>\n                      correspondingly alters M2 gene expression in macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study establishes a pan\u2010skin cancer immune remodelling framework, providing a foundation for biomarker discovery and the development of new immunotherapy strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70611","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:22:10Z","timestamp":1770200530000},"source":"Crossref","is-referenced-by-count":1,"title":["Integrative single\u2010cell analysis uncovers distinct tumour\u00a0microenvironment ecotypes and immune evasion across skin cancers"],"prefix":"10.1002","volume":"16","author":[{"given":"Lingjuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Fralin Biomedical Research Institute Virginia Tech FBRI Cancer Research Center  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nanfang hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research Center Medical Pathology Center Cancer Early Detection and Treatment Center and Translational Medicine Research Center Chongqing University Three Gorges 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