biostudies-literatureUnknownJackson MTNIDA NIH HHSNIAID NIH HHSNHLBI NIH HHSNational Institute for Health Research (NIHR)ORFDO NIH HHSWellcome TrustImproving responses to cancer immunotherapies requires deeper insight into the cellular mechanisms governing T cell-mediated anti-tumor immunity. TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types, with reported functions in anti-viral immunity as well as calcium and lipid homeostasis, yet its role in tumor immunosurveillance remains unknown. Using murine genetic models, we demonstrate that host TMEM33 constrains anti-tumor CD8⁺ T cell responses. Constitutive <i>Tmem33</i> ^<i>-/-</i> mice exhibited delayed melanoma tumor growth and increased CD8⁺ T cell infiltration. Antigen-specific CD8⁺ compartments in tumors of <i>Tmem33</i> ^<i>-/-</i> mice showed TCF-1⁺PD-1⁺ bioRxiv : the preprint server for biology2026.01.01.697288https://www.ebi.ac.uk/biostudies/studies/S-EPMC12776282biostudies-literatureTMEM33 deletion potentiates anti-tumor CD8&lt;sup&gt;+&lt;/sup&gt; T cell immunity.PMC1277628275N99020D0000575N95020D00005NIHR20331175N93022D0000575N92020D0000575N93023D00005Panetti SWithers DRAlmeida VPZhao TBeernaert BKwon JTElliott TPhyu SMGrover AZierhut CWillis CPedroza-Pacheco IParkes EEEstephan HAdamopoulou EHonore EFairfax BPJackson MTMilotay GCai YGabrilovich DIAggelakopoulou MSim MJChristianson JCRehwinkel JfalseTMEM33 deletion potentiates anti-tumor CD8&lt;sup&gt;+&lt;/sup&gt; T cell immunity.Improving responses to cancer immunotherapies requires deeper insight into the cellular mechanisms governing T cell-mediated anti-tumor immunity. TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types, with reported functions in anti-viral immunity as well as calcium and lipid homeostasis, yet its role in tumor immunosurveillance remains unknown. Using murine genetic models, we demonstrate that host TMEM33 constrains anti-tumor CD8⁺ T cell responses. Constitutive <i>Tmem33</i> ^<i>-/-</i> mice exhibited delayed melanoma tumor growth and increased CD8⁺ T cell infiltration. Antigen-specific CD8⁺ compartments in tumors of <i>Tmem33</i> ^<i>-/-</i> mice showed TCF-1⁺PD-1⁺ 2026-01-01T00:00:00Z2026 Jan2026-06-10T03:10:21.438Z2026-06-10T03:07:18.917ZS-EPMC127762824150928010.64898/2026.01.01.697288