biostudies-literatureUnknown14(1)Wang L<h4>Background</h4>Insufficient infiltration of CD8⁺ T cells in the tumor microenvironment (TME) critically restricts antitumor immunity and cancer immunotherapy efficacy. The purpose of this study was to identify novel tumor cell-intrinsic regulators of T-cell infiltration and to elucidate their mechanisms of action.<h4>Methods</h4>We performed a genome-wide Sleeping Beauty transposon mutagenesis screen in murine breast cancer models. Protein-protein interactions were identified by mass spectrometry and validated by co-immunoprecipitation. Gene and protein expression levels were assessed by reverse transcription and quantitative PCR and western blotting. T-cell infiltration and function were evaluated using flow cytometry, immunohistochemistry (IHC), multiplex IHC, and by analyJournal for immunotherapy of cancere013142https://www.ebi.ac.uk/biostudies/studies/S-EPMC12853559biostudies-literatureDUSP22 dephosphorylates LGALS1 to enhance T cell-driven antitumor immunity.PMC12853559Shao FLi JZhou NMa LGuo YDeng CXLei HFeng YSun WDai YWang LMiao KLi YPan JLuo PHong YHuang XZeng JChen WChen SSun HXu XZhang AfalseDUSP22 dephosphorylates LGALS1 to enhance T cell-driven antitumor immunity.<h4>Background</h4>Insufficient infiltration of CD8⁺ T cells in the tumor microenvironment (TME) critically restricts antitumor immunity and cancer immunotherapy efficacy. The purpose of this study was to identify novel tumor cell-intrinsic regulators of T-cell infiltration and to elucidate their mechanisms of action.<h4>Methods</h4>We performed a genome-wide Sleeping Beauty transposon mutagenesis screen in murine breast cancer models. Protein-protein interactions were identified by mass spectrometry and validated by co-immunoprecipitation. Gene and protein expression levels were assessed by reverse transcription and quantitative PCR and western blotting. T-cell infiltration and function were evaluated using flow cytometry, immunohistochemistry (IHC), multiplex IHC, and by analy2026-01-01T00:00:00Z2026 Jan2026-06-09T05:45:55.699Z2026-06-09T03:08:03.057ZS-EPMC128535594161124410.1136/jitc-2025-013142