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However, only a small portion of patients benefit from ICB therapy, indicating that the mechanism underlying immune checkpoint is still unclear. Here, it is reported that motor neuron and pancreas homeobox 1 (MNX1), a homeobox domain\u2010containing transcription factor, contributes\u00a0to the tumor immune escape. MNX1 increases PD\u2010L1 expression in cancer cells by stabilizing PD\u2010L1 mRNA rather than activating transcription. Mechanistically, MNX1 exists in the cytoplasm of cancer cells and interacts with Y\u2010box binding protein 1 (YBX1), a multifunctional DNA\/RNA\u2010binding protein, to enhance the binding of YBX1 to PD\u2010L1 mRNA. MNX1 ablation activates cytotoxic T cell\u2010mediated anti\u2010tumor immunity and sensitizes CTLA\u20104 blockade therapy. Moreover, MNX1 also facilitates tumor progression in an immune\u2010independent manner in cancer cells. In addition, MNX1 is upregulated by its adjacent long non\u2010coding RNA MNX1\u2010AS1 via HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2). Together, these results reveal MNX1 as a novel immune checkpoint regulator with promising therapeutic potential.<\/jats:p>","DOI":"10.1002\/advs.202403077","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T06:41:10Z","timestamp":1738824070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of MNX1 Sensitizes Tumors to Cytotoxic T Cells by Degradation of PD\u2010L1 mRNA"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhengzheng","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Cancer Stem Cell Dalian Medical University  Dalian 116044 China"},{"name":"Soochow University Cancer Institute  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Cancer Stem Cell Dalian Medical University  Dalian 116044 China"},{"name":"Department of Pulmonary 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