{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:59:26Z","timestamp":1789610366419,"version":"build-2803163510"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA290720"],"award-info":[{"award-number":["R01 CA290720"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA290720"],"award-info":[{"award-number":["R01 CA290720"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-20-1-0068"],"award-info":[{"award-number":["W81XWH-20-1-0068"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-20-1-0068"],"award-info":[{"award-number":["W81XWH-20-1-0068"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Biomed. Eng"],"DOI":"10.1038\/s41551-026-01720-9","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:03:04Z","timestamp":1781600584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Programmable mRNA 3\u2032UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer"],"prefix":"10.1038","author":[{"given":"Furong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-2504","authenticated-orcid":false,"given":"Fuwen","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-0928","authenticated-orcid":false,"given":"Ya","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-2544","authenticated-orcid":false,"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7811-2710","authenticated-orcid":false,"given":"Wenbin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5223-930X","authenticated-orcid":false,"given":"Zhifen","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-1155","authenticated-orcid":false,"given":"Christopher","family":"Nicchitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7883-1937","authenticated-orcid":false,"given":"Yuebao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hankey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-6284","authenticated-orcid":false,"given":"Jeffrey","family":"Everitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Lieh","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-3499","authenticated-orcid":false,"given":"Mu-En","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-1062","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-1998","authenticated-orcid":false,"given":"Jiaoti","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-383X","authenticated-orcid":false,"given":"Eric J.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-6478","authenticated-orcid":false,"given":"Xin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-0659","authenticated-orcid":false,"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9931-5990","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2636-7145","authenticated-orcid":false,"given":"Qianben","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"1720_CR1","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41571-023-00789-4","volume":"20","author":"K Yang","year":"2023","unstructured":"Yang, K., Halima, A. & Chan, T. A. Antigen presentation in cancer \u2013 mechanisms and clinical implications for immunotherapy. Nat. Rev. Clin. Oncol. 20, 604\u2013623 (2023).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1720_CR2","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/S1470-2045(14)70189-5","volume":"15","author":"ED Kwon","year":"2014","unstructured":"Kwon, E. D. et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 15, 700\u2013712 (2014).","journal-title":"Lancet Oncol."},{"key":"1720_CR3","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1200\/JCO.2016.69.1584","volume":"35","author":"TM Beer","year":"2017","unstructured":"Beer, T. M. et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J. Clin. Oncol. 35, 40\u201347 (2017).","journal-title":"J. Clin. Oncol."},{"key":"1720_CR4","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1200\/JCO.19.01638","volume":"38","author":"ES Antonarakis","year":"2020","unstructured":"Antonarakis, E. S. et al. Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 Study. J. Clin. Oncol. 38, 395\u2013405 (2020).","journal-title":"J. Clin. Oncol."},{"key":"1720_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2021.108707","volume":"226","author":"J Majidpoor","year":"2021","unstructured":"Majidpoor, J. & Mortezaee, K. The efficacy of PD-1\/PD-L1 blockade in cold cancers and future perspectives. Clin. Immunol. 226, 108707 (2021).","journal-title":"Clin. Immunol."},{"key":"1720_CR6","doi-asserted-by":"publisher","unstructured":"Rodig, S. J. et al. MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.aar3342 (2018).","DOI":"10.1126\/scitranslmed.aar3342"},{"key":"1720_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636568","volume":"12","author":"K Dhatchinamoorthy","year":"2021","unstructured":"Dhatchinamoorthy, K., Colbert, J. D. & Rock, K. L. Cancer immune evasion through loss of MHC class I antigen presentation. Front. Immunol. 12, 636568 (2021).","journal-title":"Front. Immunol."},{"key":"1720_CR8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.gendis.2019.10.011","volume":"8","author":"F Yuan","year":"2021","unstructured":"Yuan, F., Hankey, W., Wagner, E. J., Li, W. & Wang, Q. Alternative polyadenylation of mRNA and its role in cancer. Genes Dis. 8, 61\u201372 (2021).","journal-title":"Genes Dis."},{"key":"1720_CR9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrm.2016.116","volume":"18","author":"B Tian","year":"2017","unstructured":"Tian, B. & Manley, J. L. Alternative polyadenylation of mRNA precursors. Nat. Rev. Mol. Cell Biol. 18, 18\u201330 (2017).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1720_CR10","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41576-019-0145-z","volume":"20","author":"AJ Gruber","year":"2019","unstructured":"Gruber, A. J. & Zavolan, M. Alternative cleavage and polyadenylation in health and disease. Nat. Rev. Genet. 20, 599\u2013614 (2019).","journal-title":"Nat. Rev. Genet."},{"key":"1720_CR11","doi-asserted-by":"publisher","unstructured":"Mayr, C. What Are 3\u2032 UTRs Doing? Cold Spring Harb. Perspect. Biol. https:\/\/doi.org\/10.1101\/cshperspect.a034728 (2019).","DOI":"10.1101\/cshperspect.a034728"},{"key":"1720_CR12","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/nrg3482","volume":"14","author":"R Elkon","year":"2013","unstructured":"Elkon, R., Ugalde, A. P. & Agami, R. Alternative cleavage and polyadenylation: extent, regulation and function. Nat. Rev. Genet. 14, 496\u2013506 (2013).","journal-title":"Nat. Rev. Genet."},{"key":"1720_CR13","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nature13261","volume":"510","author":"CP Masamha","year":"2014","unstructured":"Masamha, C. P. et al. CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature 510, 412\u2013416 (2014).","journal-title":"Nature"},{"key":"1720_CR14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.cell.2009.06.016","volume":"138","author":"C Mayr","year":"2009","unstructured":"Mayr, C. & Bartel, D. P. Widespread shortening of 3\u2032UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138, 673\u2013684 (2009).","journal-title":"Cell"},{"key":"1720_CR15","doi-asserted-by":"publisher","first-page":"5274","DOI":"10.1038\/ncomms6274","volume":"5","author":"Z Xia","year":"2014","unstructured":"Xia, Z. et al. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3\u2032-UTR landscape across seven tumour types. Nat. Commun. 5, 5274 (2014).","journal-title":"Nat. Commun."},{"key":"1720_CR16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41579-019-0299-x","volume":"18","author":"KS Makarova","year":"2020","unstructured":"Makarova, K. S. et al. Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat. Rev. Microbiol. 18, 67\u201383 (2020).","journal-title":"Nat. Rev. Microbiol."},{"key":"1720_CR17","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1126\/science.aaq0180","volume":"358","author":"DBT Cox","year":"2017","unstructured":"Cox, D. B. T. et al. RNA editing with CRISPR-Cas13. Science 358, 1019\u20131027 (2017).","journal-title":"Science"},{"key":"1720_CR18","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.cell.2018.02.033","volume":"173","author":"S Konermann","year":"2018","unstructured":"Konermann, S. et al. Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell 173, 665\u2013676.e14 (2018).","journal-title":"Cell"},{"key":"1720_CR19","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1038\/s41587-020-0572-6","volume":"38","author":"C Wilson","year":"2020","unstructured":"Wilson, C., Chen, P. J., Miao, Z. & Liu, D. R. Programmable m6A modification of cellular RNAs with a Cas13-directed methyltransferase. Nat. Biotechnol. 38, 1431\u20131440 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1720_CR20","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.molcel.2019.10.024","volume":"76","author":"LZ Yang","year":"2019","unstructured":"Yang, L. Z. et al. Dynamic imaging of RNA in living cells by CRISPR-Cas13 systems. Mol. Cell 76, 981\u2013997.e7 (2019).","journal-title":"Mol. Cell"},{"key":"1720_CR21","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1093\/nar\/gkac108","volume":"50","author":"S Tian","year":"2022","unstructured":"Tian, S. et al. CRISPR-iPAS: a novel dCAS13-based method for alternative polyadenylation interference. Nucleic Acids Res. 50, e26 (2022).","journal-title":"Nucleic Acids Res."},{"key":"1720_CR22","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1126\/science.1235122","volume":"339","author":"B Vogelstein","year":"2013","unstructured":"Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546\u20131558 (2013).","journal-title":"Science"},{"key":"1720_CR23","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1126\/science.aab4082","volume":"349","author":"I Martincorena","year":"2015","unstructured":"Martincorena, I. & Campbell, P. J. Somatic mutation in cancer and normal cells. Science 349, 1483\u20131489 (2015).","journal-title":"Science"},{"key":"1720_CR24","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.cell.2015.10.025","volume":"163","author":"Cancer Genome Atlas Research Network.","year":"2015","unstructured":"Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell 163, 1011\u20131025 (2015).","journal-title":"Cell"},{"key":"1720_CR25","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nm.4045","volume":"22","author":"H Beltran","year":"2016","unstructured":"Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298\u2013305 (2016).","journal-title":"Nat. Med."},{"key":"1720_CR26","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","volume":"161","author":"D Robinson","year":"2015","unstructured":"Robinson, D. et al. Integrative clinical genomics of advanced prostate cancer. Cell 161, 1215\u20131228 (2015).","journal-title":"Cell"},{"key":"1720_CR27","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.eururo.2014.09.019","volume":"67","author":"JA Brockman","year":"2015","unstructured":"Brockman, J. A. et al. Nomogram predicting prostate cancer-specific mortality for men with biochemical recurrence after radical prostatectomy. Eur. Urol. 67, 1160\u20131167 (2015).","journal-title":"Eur. Urol."},{"key":"1720_CR28","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/s41580-022-00507-5","volume":"23","author":"S Mitschka","year":"2022","unstructured":"Mitschka, S. & Mayr, C. Context-specific regulation and function of mRNA alternative polyadenylation. Nat. Rev. Mol. Cell Biol. 23, 779\u2013796 (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1720_CR29","doi-asserted-by":"publisher","first-page":"D247","DOI":"10.1093\/nar\/gkaf1212","volume":"54","author":"S Yu","year":"2025","unstructured":"Yu, S. et al. PolyA_DB v4: systematic polyA site identification and isoform annotation in human and mouse genomes using 3\u2032 end and long-read sequencing data. Nucleic Acids Res. 54, D247\u2013D254 (2025).","journal-title":"Nucleic Acids Res."},{"key":"1720_CR30","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.cell.2012.03.022","volume":"149","author":"M Jenal","year":"2012","unstructured":"Jenal, M. et al. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell 149, 538\u2013553 (2012).","journal-title":"Cell"},{"key":"1720_CR31","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/978-1-62703-971-0_14","volume":"1125","author":"AL Cornett","year":"2014","unstructured":"Cornett, A. L. & Lutz, C. S. RHAPA: a new method to quantify alternative polyadenylation. Methods Mol. Biol. 1125, 157\u2013167 (2014).","journal-title":"Methods Mol. Biol."},{"key":"1720_CR32","doi-asserted-by":"publisher","first-page":"8099","DOI":"10.1021\/acs.nanolett.5b03528","volume":"15","author":"B Li","year":"2015","unstructured":"Li, B. et al. An orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo. Nano Lett. 15, 8099\u20138107 (2015).","journal-title":"Nano Lett."},{"key":"1720_CR33","doi-asserted-by":"publisher","unstructured":"Agarwal, S. et al. Tumor-derived biomarkers predict efficacy of B7H3 antibody-drug conjugate treatment in metastatic prostate cancer models. J. Clin. Invest. https:\/\/doi.org\/10.1172\/jci162148 (2023).","DOI":"10.1172\/jci162148"},{"key":"1720_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217432","volume":"611","author":"S Kong","year":"2024","unstructured":"Kong, S. et al. Mechanisms of low MHC I expression and strategies for targeting MHC I with small molecules in cancer immunotherapy. Cancer Lett. 611, 217432 (2024).","journal-title":"Cancer Lett."},{"key":"1720_CR35","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1073\/pnas.95.1.114","volume":"95","author":"DJ Hilton","year":"1998","unstructured":"Hilton, D. J. et al. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc. Natl Acad. Sci. USA 95, 114\u2013119 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1720_CR36","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/iub.1011","volume":"64","author":"EM Linossi","year":"2012","unstructured":"Linossi, E. M. & Nicholson, S. E. The SOCS box-adapting proteins for ubiquitination and proteasomal degradation. IUBMB Life 64, 316\u2013323 (2012).","journal-title":"IUBMB Life"},{"key":"1720_CR37","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0968-0004(02)02085-6","volume":"27","author":"BT Kile","year":"2002","unstructured":"Kile, B. T. et al. The SOCS box: a tale of destruction and degradation. Trends Biochem. Sci. 27, 235\u2013241 (2002).","journal-title":"Trends Biochem. Sci."},{"key":"1720_CR38","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade4656","volume":"8","author":"Y Zhu","year":"2023","unstructured":"Zhu, Y. et al. Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer. Sci. Immunol. 8, eade4656 (2023).","journal-title":"Sci. Immunol."},{"key":"1720_CR39","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/nature21676","volume":"543","author":"X Lu","year":"2017","unstructured":"Lu, X. et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543, 728\u2013732 (2017).","journal-title":"Nature"},{"key":"1720_CR40","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1158\/2159-8290.CD-20-0812","volume":"11","author":"SS Gu","year":"2021","unstructured":"Gu, S. S. et al. Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade. Cancer Discov. 11, 1524\u20131541 (2021).","journal-title":"Cancer Discov."},{"key":"1720_CR41","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-022-00601-9","volume":"19","author":"H Yamaguchi","year":"2022","unstructured":"Yamaguchi, H., Hsu, J. M., Yang, W. H. & Hung, M. C. Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics. Nat. Rev. Clin. Oncol. 19, 287\u2013305 (2022).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1720_CR42","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/s41577-020-0390-6","volume":"21","author":"D Dersh","year":"2021","unstructured":"Dersh, D., Holl\u00fd, J. & Yewdell, J. W. A few good peptides: MHC class I-based cancer immunosurveillance and immunoevasion. Nat. Rev. Immunol. 21, 116\u2013128 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"1720_CR43","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.it.2024.01.009","volume":"45","author":"J Wang","year":"2024","unstructured":"Wang, J., Lu, Q., Chen, X. & Aifantis, I. Targeting MHC-I inhibitory pathways for cancer immunotherapy. Trends Immunol. 45, 177\u2013187 (2024).","journal-title":"Trends Immunol."},{"key":"1720_CR44","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","volume":"76","author":"KA Hogquist","year":"1994","unstructured":"Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17\u201327 (1994).","journal-title":"Cell"},{"key":"1720_CR45","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1172\/JCI91190","volume":"127","author":"M Ayers","year":"2017","unstructured":"Ayers, M. et al. IFN-\u03b3-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Invest. 127, 2930\u20132940 (2017).","journal-title":"J. Clin. Invest."},{"key":"1720_CR46","doi-asserted-by":"publisher","first-page":"25194","DOI":"10.18632\/oncotarget.7535","volume":"7","author":"A Saha","year":"2016","unstructured":"Saha, A., Blando, J., Fernandez, I., Kiguchi, K. & DiGiovanni, J. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo. Oncotarget 7, 25194\u201325207 (2016).","journal-title":"Oncotarget"},{"key":"1720_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12464-3","volume":"10","author":"PA Szabo","year":"2019","unstructured":"Szabo, P. A. et al. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat. Commun. 10, 4706 (2019).","journal-title":"Nat. Commun."},{"key":"1720_CR48","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1038\/s12276-023-01105-x","volume":"55","author":"CH Koh","year":"2023","unstructured":"Koh, C. H., Lee, S., Kwak, M., Kim, B. S. & Chung, Y. CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential. Exp. Mol. Med. 55, 2287\u20132299 (2023).","journal-title":"Exp. Mol. Med."},{"key":"1720_CR49","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","volume":"18","author":"J Galon","year":"2019","unstructured":"Galon, J. & Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 18, 197\u2013218 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1720_CR50","doi-asserted-by":"publisher","first-page":"6764","DOI":"10.1158\/1078-0432.CCR-17-0019","volume":"23","author":"M Bilusic","year":"2017","unstructured":"Bilusic, M., Madan, R. A. & Gulley, J. L. Immunotherapy of prostate cancer: facts and hopes. Clin. Cancer Res. 23, 6764\u20136770 (2017).","journal-title":"Clin. Cancer Res."},{"key":"1720_CR51","doi-asserted-by":"publisher","first-page":"171","DOI":"10.4103\/aja202283","volume":"25","author":"Y Zhu","year":"2023","unstructured":"Zhu, Y., Duong, L., Lu, X. & Lu, X. Cancer-cell-intrinsic mechanisms shaping the immunosuppressive landscape of prostate cancer. Asian J. Androl. 25, 171\u2013178 (2023).","journal-title":"Asian J. Androl."},{"key":"1720_CR52","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1001\/jamaoncol.2018.5801","volume":"5","author":"W Abida","year":"2019","unstructured":"Abida, W. et al. Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol. 5, 471\u2013478 (2019).","journal-title":"JAMA Oncol."},{"key":"1720_CR53","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1158\/2159-8290.CD-24-0559","volume":"15","author":"LN Chesner","year":"2025","unstructured":"Chesner, L. N. et al. Androgen receptor inhibition increases MHC class I expression and improves immune response in prostate cancer. Cancer Discov. 15, 481\u2013494 (2025).","journal-title":"Cancer Discov."},{"key":"1720_CR54","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/pros.24110","volume":"81","author":"E Shenderov","year":"2021","unstructured":"Shenderov, E. et al. Nivolumab plus ipilimumab, with or without enzalutamide, in AR-V7-expressing metastatic castration-resistant prostate cancer: a phase-2 nonrandomized clinical trial. Prostate 81, 326\u2013338 (2021).","journal-title":"Prostate"},{"key":"1720_CR55","doi-asserted-by":"publisher","first-page":"S957","DOI":"10.1016\/j.annonc.2023.09.2721","volume":"34","author":"JN Graff","year":"2023","unstructured":"Graff, J. N. et al. 1771MO pembrolizumab (pembro) plus enzalutamide (enza) for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): randomized double-blind phase III KEYNOTE-641 study. Ann. Oncol. 34, S957 (2023).","journal-title":"Ann. Oncol."},{"key":"1720_CR56","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41568-021-00339-z","volume":"21","author":"S Jhunjhunwala","year":"2021","unstructured":"Jhunjhunwala, S., Hammer, C. & Delamarre, L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat. Rev. Cancer 21, 298\u2013312 (2021).","journal-title":"Nat. Rev. Cancer"},{"key":"1720_CR57","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/j.trecan.2021.07.006","volume":"7","author":"L Maggs","year":"2021","unstructured":"Maggs, L., Sadagopan, A., Moghaddam, A. S. & Ferrone, S. HLA class I antigen processing machinery defects in antitumor immunity and immunotherapy. Trends Cancer 7, 1089\u20131101 (2021).","journal-title":"Trends Cancer"},{"key":"1720_CR58","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","volume":"52","author":"PS Hegde","year":"2020","unstructured":"Hegde, P. S. & Chen, D. S. Top 10 challenges in cancer immunotherapy. Immunity 52, 17\u201335 (2020).","journal-title":"Immunity"},{"key":"1720_CR59","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.coi.2015.12.007","volume":"39","author":"F Garrido","year":"2016","unstructured":"Garrido, F., Aptsiauri, N., Doorduijn, E. M., Garcia Lora, A. M. & van Hall, T. The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr. Opin. Immunol. 39, 44\u201351 (2016).","journal-title":"Curr. Opin. Immunol."},{"key":"1720_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102329","volume":"83","author":"G Sari","year":"2023","unstructured":"Sari, G. & Rock, K. L. Tumor immune evasion through loss of MHC class-I antigen presentation. Curr. Opin. Immunol. 83, 102329 (2023).","journal-title":"Curr. Opin. Immunol."},{"key":"1720_CR61","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.1016\/j.cell.2023.07.016","volume":"186","author":"X Chen","year":"2023","unstructured":"Chen, X. et al. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell 186, 3903\u20133920.e21 (2023).","journal-title":"Cell"},{"key":"1720_CR62","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/nmeth854","volume":"3","author":"A Birmingham","year":"2006","unstructured":"Birmingham, A. et al. 3\u2019 UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3, 199\u2013204 (2006).","journal-title":"Nat. Methods"},{"key":"1720_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201901299","volume":"6","author":"Q Wang","year":"2019","unstructured":"Wang, Q. et al. The CRISPR-Cas13a gene-editing system induces collateral cleavage of RNA in glioma cells. Adv. Sci. 6, 1901299 (2019).","journal-title":"Adv. Sci."},{"key":"1720_CR64","doi-asserted-by":"crossref","unstructured":"Keep off-target effects in focus. Nat. Med. 24, 1081 (2018).","DOI":"10.1038\/s41591-018-0150-3"},{"key":"1720_CR65","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","volume":"25","author":"CT Charlesworth","year":"2019","unstructured":"Charlesworth, C. T. et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat. Med. 25, 249\u2013254 (2019).","journal-title":"Nat. Med."},{"key":"1720_CR66","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.immuni.2018.03.004","volume":"48","author":"MD Wellenstein","year":"2018","unstructured":"Wellenstein, M. D. & de Visser, K. E. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity 48, 399\u2013416 (2018).","journal-title":"Immunity"},{"key":"1720_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2032","volume":"3","author":"H Rhinn","year":"2012","unstructured":"Rhinn, H. et al. Alternative \u03b1-synuclein transcript usage as a convergent mechanism in Parkinson\u2019s disease pathology. Nat. Commun. 3, 1084 (2012).","journal-title":"Nat. Commun."},{"key":"1720_CR68","doi-asserted-by":"publisher","unstructured":"Zhang, X. et al. Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing. Sci. Adv. https:\/\/doi.org\/10.1126\/sciadv.abc2315 (2020).","DOI":"10.1126\/sciadv.abc2315"},{"key":"1720_CR69","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","volume":"15","author":"Q Cheng","year":"2020","unstructured":"Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313\u2013320 (2020).","journal-title":"Nat. Nanotechnol."},{"key":"1720_CR70","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.vetmic.2009.12.046","volume":"144","author":"HE Booij-Vrieling","year":"2010","unstructured":"Booij-Vrieling, H. E. et al. Comparison of periodontal pathogens between cats and their owners. Vet. Microbiol. 144, 147\u2013152 (2010).","journal-title":"Vet. Microbiol."},{"key":"1720_CR71","doi-asserted-by":"publisher","first-page":"6810","DOI":"10.1073\/pnas.1718811115","volume":"115","author":"Z Chen","year":"2018","unstructured":"Chen, Z. et al. Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13. Proc. Natl Acad. Sci. USA 115, 6810\u20136815 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1720_CR72","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/ng.3470","volume":"48","author":"X Zhang","year":"2016","unstructured":"Zhang, X. et al. Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat. Genet. 48, 176\u2013182 (2016).","journal-title":"Nat. Genet."},{"key":"1720_CR73","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"GTEx Consortium","year":"2013","unstructured":"GTEx Consortium The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580\u2013585 (2013).","journal-title":"Nat. Genet."},{"key":"1720_CR74","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1126\/science.aad0095","volume":"350","author":"EM Van Allen","year":"2015","unstructured":"Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207\u2013211 (2015).","journal-title":"Science"},{"key":"1720_CR75","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1038\/s41591-019-0654-5","volume":"25","author":"D Liu","year":"2019","unstructured":"Liu, D. et al. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nat. Med. 25, 1916\u20131927 (2019).","journal-title":"Nat. Med."},{"key":"1720_CR76","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41586-022-04522-6","volume":"606","author":"X Guan","year":"2022","unstructured":"Guan, X. et al. Androgen receptor activity in T cells limits checkpoint blockade efficacy. Nature 606, 791\u2013796 (2022).","journal-title":"Nature"},{"key":"1720_CR77","doi-asserted-by":"crossref","unstructured":"Moll, P., Ante, M., Seitz, A. & Reda, T. QuantSeq 3\u2032 mRNA sequencing for RNA quantification. Nat. Methods 11, i\u2013iii (2014).","DOI":"10.1038\/nmeth.f.376"},{"key":"1720_CR78","doi-asserted-by":"publisher","first-page":"71","DOI":"10.7171\/jbt.18-2903-002","volume":"29","author":"T Muinao","year":"2018","unstructured":"Muinao, T., Pal, M. & Boruah, H. P. D. Cytosolic and transmembrane protein extraction methods of breast and ovarian cancer cells: a comparative study. J. Biomol. Tech. 29, 71\u201378 (2018).","journal-title":"J. Biomol. Tech."},{"key":"1720_CR79","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.molcel.2010.12.032","volume":"41","author":"S Danckwardt","year":"2011","unstructured":"Danckwardt, S. et al. p38 MAPK controls prothrombin expression by regulated RNA 3\u2032 end processing. Mol. Cell 41, 298\u2013310 (2011).","journal-title":"Mol. Cell"},{"key":"1720_CR80","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/978-1-4939-3378-5_2","volume":"1402","author":"JH Yoon","year":"2016","unstructured":"Yoon, J. H. & Gorospe, M. Cross-linking immunoprecipitation and qPCR (CLIP-qPCR) analysis to map interactions between long noncoding RNAs and RNA-binding proteins. Methods Mol. Biol. 1402, 11\u201317 (2016).","journal-title":"Methods Mol. Biol."},{"key":"1720_CR81","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.cell.2015.05.014","volume":"161","author":"X Wang","year":"2015","unstructured":"Wang, X. et al. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388\u20131399 (2015).","journal-title":"Cell"},{"key":"1720_CR82","doi-asserted-by":"publisher","unstructured":"Cui, Z. et al. Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection. Nat. Chem. Biol. https:\/\/doi.org\/10.1038\/s41589-022-01094-4 (2022).","DOI":"10.1038\/s41589-022-01094-4"},{"key":"1720_CR83","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/nprot.2018.004","volume":"13","author":"B Li","year":"2018","unstructured":"Li, B., Zeng, C. & Dong, Y. Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing. Nat. Protoc. 13, 899\u2013914 (2018).","journal-title":"Nat. Protoc."},{"key":"1720_CR84","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1038\/s43018-020-0095-6","volume":"1","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat. Cancer 1, 882\u2013893 (2020).","journal-title":"Nat. Cancer"},{"key":"1720_CR85","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","volume":"50","author":"Y Perez-Riverol","year":"2022","unstructured":"Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543\u2013D552 (2022).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-026-01720-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-026-01720-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-026-01720-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:03:13Z","timestamp":1781600593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-026-01720-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":85,"alternative-id":["1720"],"URL":"https:\/\/doi.org\/10.1038\/s41551-026-01720-9","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"15 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All human data analysed in this study were obtained from publicly available, de-identified datasets (dbGaP). Human specimens and de-identified human data used in this study included archival CRPC tissue slides and commercially obtained human melanoma tissue microarrays (TissueArray, ME1006). No new human participants were recruited and no identifiable private information was accessed. The secondary use of these data was reviewed and approved by the Institutional Review Board of the University of California, Irvine (UCI IRB 431), and was determined to be in compliance with all relevant ethical regulations and data-use agreements.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declarations"}},{"value":"The research described in this manuscript is the subject of an issued patent (Q.W., W.L. and F.Y., US patent no. US 12,467,043 B2; date of patent, 11 November 2025) and a patent application (Q.W., US patent application no. 63\/944,661; filing date, 19 December 2025) filed by Duke University. J.H. is a consultant for or owns shares in the following companies: Kingmed, MoreHealth, OptraScan, Genetron, Omnitura, Vetonco, York Biotechnology, Genecode, VIVA Biotech, and Sisu Pharma, and received grants from Zenith Epigenetics, BioXcel Therapeutics, Inc., and Fortis Therapeutics. The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}