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Alliance"],"accepted":{"date-parts":[[2026,7,28]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    LIMD1, a tumour suppressor located at chromosome 3p21.3, is frequently lost in non\u2013small-cell lung cancer, yet its role in tumour\u2013immune interactions remains unclear. Here, we show LIMD1 loss increases PD-L1 protein abundance across multiple lung cancer models and primary airway epithelial cells. Mechanistically, LIMD1 restrains PD-L1 through post-transcriptional and post-translational mechanisms. LIMD1 loss can relieve microRNA-mediated repression of the\n                    <jats:italic>CD274<\/jats:italic>\n                    3\u2032UTR, and LIMD1 loss can also disrupt ARIH1-PD-L1 association, reduce PD-L1 polyubiquitination, and stabilise PD-L1 protein without a commensurate increase in\n                    <jats:italic>CD274<\/jats:italic>\n                    transcript levels in isogenic models. Functionally, LIMD1-deficient tumour cells suppress CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell activation in vitro and show enhanced sensitivity to PD-1\/PD-L1 blockade in tumour\u2013PBMC co-culture assays. Analysis of TRACERx non\u2013small-cell lung cancer samples revealed clonal LIMD1 loss of heterozygosity in \u223c40% of lung adenocarcinomas, where it is associated with increased tumour PD-L1 expression. Across independent patient cohorts receiving immune checkpoint blockade, low LIMD1 expression was enriched among responders. We identify LIMD1 as a tumour-intrinsic regulator of PD-L1 turnover and suggest that tumour suppressor loss can shape immune checkpoint biology and influence immunotherapy response.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202603812","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:21:52Z","timestamp":1785306112000},"page":"e202603812","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clonal\n                    <i>LIMD1<\/i>\n                    loss drives PD-L1 immune evasion via ARIH1-dependent ubiquitination in lung cancer"],"prefix":"10.26508","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-9606","authenticated-orcid":true,"given":"Kunal M","family":"Shah","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/026zzn846","id-type":"ROR","asserted-by":"publisher"}],"name":"The Centre for Cancer Cell and Molecular Biology, 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