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This study aims to define the spatial architecture of the melanoma TME and identify key molecular regulators that determine anti-tumor immunity and ICB response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an integrative analysis of single-cell and spatial transcriptomics to map the TME. We defined spatial domains and deconvoluted their cellular composition. Cell-cell communication and risk modeling were performed. Functional roles of candidate genes were assessed using in vitro co-culture with anti-PD-1 and in vivo knockdown in a humanized mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We delineated two prognostically significant spatial domains: an Immune region and a Melanocyte region. Multi-omics convergence nominated CORO1A as a key regulator within the immune niche. Its knockdown synergized with anti-PD-1 to suppress tumor growth in vivo, and anti-PD-1 downregulated its expression in vitro. We further identified APP-CD74 and FN1\u2013CD44 as key inter-domain communication axes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study provides a spatially resolved blueprint of the melanoma TME and identifies\n                      <jats:italic>CORO1A<\/jats:italic>\n                      as a functional regulator within the immune niche, where its modulation enhances T-cell activity and synergizes with ICB. These findings reveal spatial organization as a critical determinant of immunotherapy efficacy and nominate\n                      <jats:italic>CORO1A<\/jats:italic>\n                      as a promising target for combination therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08435-0","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:38:14Z","timestamp":1782236294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial architecture of the melanoma immune niche reveals CORO1A as a functional hub for T cell cytotoxicity and immunotherapy synergy"],"prefix":"10.1186","volume":"24","author":[{"given":"Shuai","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxinai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengxiao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4878-0264","authenticated-orcid":false,"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"issue":"1","key":"8435_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12943-023-01876-x","volume":"22","author":"Chenxi","year":"2023","unstructured":"Chenxi, Yang C, Peng A, Sun T, Ji X, Mi J, et al. 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The use of human tissue samples was approved by the same committee (Approval No. Med-Eth-Re-2025-2025601) and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all patients.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SZ, HW, JW, PF, YL, TM, and LL are affiliated with the Hainan General Hospital, Hainan Medical University.","order":3,"name":"Ethics","label":"Author information","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Generative AI and AI-assisted technologies were NOT used in the preparation of this work.","order":4,"name":"Ethics","label":"Generative AI and AI-assisted","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1159"}}