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Lysates were cleared by centrifugation at 4 °C, 48,000 ×g for 45 minutes and passed through a pre-clearing column containing Protein A Sepharose beads (GenScript). HLA-peptide complexes were then immunoaffinity purified from the cleared lysate using pan-HLA antibody (W6/32 antibody purified from HB95 hybridoma cells), covalently bound to Protein A sepharose beads. The HLA-peptide complexes were eluted with 1% trifluoracetic acid (TFA), followed by purification of the peptides by Sep-Pak tC18 100 mg Sorbent 96-well plate (Waters). Elution of the peptides was done with 28% acetonitrile (ACN) in 0.1% TFA."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["LC-MS/MS analysis The HLA peptides were dried by vacuum centrifugation, resolubilised with 0.1% TFA and 5 mM TCEP and separated using reversed-phase chromatography using the nanoElute2 system (Bruker), with the Aurora C18 nano column (75 μm × 250 mm, IonOptiks, Australia), mobile phase A: H2O + 0.1% formic acid, B: acetonitrile + 0.1% formic acid. The HLA peptides were separated with a linear gradient over 80 minutes from 2 to 29%, 28 to 95% in 0.5 minutes, maintained at 95% for 2.9 minutes and back to initial conditions, at a flow rate of 0.3 μL/minute. The chromatography system was coupled by a captive spray nanoESI to quadrupole-ion mobility-time-of-flight mass spectrometer (TIMS-ToF Pro, Bruker). The MS was operated in data de-pendent acquisition mode (DDA). Mass range of 100-1,700 Th. Ion Mobility range was set to 1/K0 start 0.6 1.57, ramp time 300 msec. Target intensity was set to 20,000 and threshold of 2,500."],"omics_type":["Proteomics"],"labhead":["Yardena Samuels"],"instrument_platform":[""],"labhead_affiliation":["Weizmann Institute of Science"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["chen.weller@weizmann.ac.il"],"publication":["10.1016/J.IMMUNI.2026.02.005."],"submitter_affiliation":["Yardena Samuels lab, Weizmann Institute of Science"],"submitter_country":["Israel"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological inhibition of nonsense-mediated mRNA decay enhances anti-tumor immunity","description":"Frameshift insertion/deletions can produce highly immunogenic neoantigens; however, frameshift-derived transcripts are often degraded by the nonsense-mediated mRNA decay (NMD) pathway. Leveraging multiomics and checkpoint in-hibitor (CPI) response data from over 1,000 patients, we demonstrate that reduced expression or genetic loss of the NMD mediator SMG1 correlates with improved CPI responses. SMG1 inhibition ex vivo and in vivo activates and expands tumour-reactive lymphocytes and potentiates CPI responses. Mechanistically, SMG1 inhibi-tion stabilises frameshift-derived transcripts and increases the abundance and sur-face presentation of immunogenic neoantigens, shifting the neoepitope count from a low- to a high-tumour mutational burden (TMB)-like state without causing DNA damage. Co-culture of lymphocytes with tumour cells upon SMG1i induces antigen-dependent T cell activation and tumour cell killing. Our findings highlight SMG1 in-hibition as a promising immuno-oncology strategy to harness an untapped source of immunogenic neoantigens to enhance tumour immunogenicity and improve CPI efficacy, with broad applicability irrespective of TMB status.","dates":{"publication":"2026-04-07","submission":"2026-01-20"},"accession":"PXD073256","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:184922","NEWT:6703","NEWT:3555","NEWT:71647","NEWT:2","NEWT:157546","NEWT:474186","NEWT:35554","NEWT:38942","NEWT:307972","NEWT:32046","NEWT:1496","NEWT:544496","NEWT:2102","NEWT:2042546","NEWT:259447","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:4513","NEWT:180454","NEWT:5722","NEWT:1247","NEWT:6938","NEWT:1129","NEWT:55153","NCBITaxon:10407","NEWT:1736309","NEWT:309800","NEWT:281395","NEWT:10360","NEWT:1211601","NEWT:876138","NEWT:47664","NEWT:317548","NEWT:3654","NEWT:237561","NEWT:5833","NEWT:6928","NEWT:10036","NEWT:36745","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:272563","NEWT:1147161","NEWT:224326","NEWT:1333499","NCBITaxon:79857","NEWT:1096976","NEWT:82688","NEWT:95648","NEWT:3885","NEWT:3888","NEWT:5821","NEWT:1589","NEWT:44139","NEWT:135622","NCBITaxon:4896","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:28903","NEWT:3880","NEWT:272559","NEWT:28909","NEWT:515849","NEWT:3641","NEWT:383379","NEWT:466585","NEWT:10029","NEWT:913645","NEWT:1000589","NEWT:85963","NEWT:85962","NEWT:143361","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:398580","NEWT:4442","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:192875","NEWT:34305","NEWT:59729","NEWT:2164133","NCBITaxon:183674","NEWT:1316931","NEWT:224308","NEWT:167387","NEWT:84645","NEWT:44586","NEWT:626528","NEWT:3347","NEWT:511145","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:5888","NEWT:211586","NEWT:747078","NEWT:1282","NEWT:1283","NEWT:431241","NEWT:931281","NEWT:4550","NEWT:1000561","NEWT:2133","NEWT:294381","NEWT:197","NEWT:1390363","NEWT:77133","NEWT:288705","NEWT:29176","NEWT:145481","NCBITaxon:79824","NEWT:4787","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:556182","NEWT:1270","NEWT:374990","NEWT:1392","NEWT:498217","NEWT:156471","NEWT:2242","NEWT:4784","NEWT:11320","NEWT:360106","NEWT:156476","NEWT:286","NEWT:391619","NEWT:360104","NEWT:246196","NEWT:287","NEWT:246197","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:10358","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:44685","NEWT:317513","NEWT:161934","NEWT:1148","NEWT:580240","NEWT:5508","NEWT:294128","NEWT:5507","NEWT:11676","NEWT:55571","NEWT:35500","NEWT:1140","NEWT:100226","NEWT:4530","NEWT:1143","NEWT:4896","NEWT:75058","NEWT:13616","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1336795","NEWT:644042","NEWT:296543","NEWT:316435","NEWT:42157","NEWT:1773","NEWT:1895","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:1034304","NEWT:105023","NEWT:866628","NEWT:935293","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:375146","NEWT:9378","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:263","NEWT:230741","NEWT:52283","NEWT:284812","NEWT:8175","NCBITaxon:1313","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44544","NEWT:47946","NEWT:4911","NEWT:645463","NEWT:3702","NEWT:129249","NEWT:1077286","NEWT:943129","NEWT:243277","NEWT:990119","NEWT:7067","NEWT:2850","NEWT:1111708","NEWT:408172","NEWT:227321","NEWT:408170","NEWT:493760","NEWT:106590","NEWT:260710","NEWT:257313","NEWT:3827","NEWT:400772","NEWT:3708","NEWT:128161","NEWT:332648","NEWT:930945","NEWT:106592","NEWT:536231","NEWT:46704","NEWT:1436733","NEWT:460519","NEWT:1187947","NEWT:572307","NEWT:1432138","NEWT:269796","NEWT:10312","NEWT:1424507","NCBITaxon:1773","NEWT:1194599","NEWT:272844","NEWT:54571","NEWT:9598","NEWT:8030","NEWT:9483","NEWT:1513458","NCBITaxon:40559","NEWT:1639","NEWT:84588","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:759272","NEWT:432359","NEWT:46835","NEWT:1182263","NEWT:109757","NEWT:943146","NEWT:2711","NEWT:300852","NEWT:537457","NEWT:1502","NEWT:376686","NEWT:95486","NEWT:9103","NEWT:508771","NEWT:1883446","NEWT:29159","NEWT:253","NEWT:10306","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:8022","NEWT:145943","NCBITaxon:4932","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:89920","NEWT:29158","NEWT:644223","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:180923","NEWT:108458","NEWT:272623","NEWT:272624","NEWT:411483","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:983964","NEWT:118499","NEWT:169963","NEWT:32644","NEWT:527796","NEWT:225117","NEWT:746128","NEWT:499175","NEWT:109779","NEWT:43665","NEWT:1266464","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:367830","NEWT:1255228","NEWT:178616","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:375451","NEWT:352472","NEWT:357","NEWT:1071661","NEWT:360094","NEWT:470","NEWT:41364","NEWT:1313","NEWT:411469","NEWT:84023","NEWT:1679","NEWT:559292","NEWT:39491","NCBITaxon:5811","NEWT:29491","NEWT:411464","NEWT:411460","NEWT:2014887","NEWT:2762","NEWT:1174673","NEWT:1328426","NEWT:562","NEWT:411470","NEWT:33952","NEWT:2094720","NCBITaxon:2697049","NEWT:571256","NCBITaxon:138","NEWT:40483","NEWT:28038","NEWT:1663","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2759",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