{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:43:34Z","timestamp":1793119414609,"version":"4.5.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Antigen cross-presentation is essential for initiating CD8\n                    <jats:sup>\n                      <jats:bold>+<\/jats:bold>\n                    <\/jats:sup>\n                    cytotoxic T lymphocyte (CTL) response. Perforin-2 (P2), a pore-forming protein constitutively expressed in dendritic cells (DCs), has been implicated in endocytic cargo escape, but its role in cross-presentation remains poorly defined. Here, we show that loss of P2 markedly impairs DC-mediated cross-presentation of both soluble and particulate antigens, leading to weakened antigen-specific CD8\n                    <jats:sup>\n                      <jats:bold>+<\/jats:bold>\n                    <\/jats:sup>\n                    T cell responses. Additionally,\n                    <jats:italic>P2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice exhibited defective endogenous CTL responses and diminished anti-tumor immunity in melanoma models. Mechanistically, oligomerization of plasma membrane P2 promotes antigen uptake via membrane-repair-mediated macropinocytosis. In parallel, P2 limits excessive endosomal acidification, preserving antigens for efficient loading onto MHC class I molecules. These findings identify P2 as a key regulator that coordinates antigen uptake and processing to support effective cross-presentation and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunity.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08705-1","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T02:25:26Z","timestamp":1775701526000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perforin-2 enhances antigen-specific CTL immune response by promoting cross presentation"],"prefix":"10.1038","volume":"17","author":[{"given":"Zhi-kai","family":"Zha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-jie","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-jun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-zhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-xiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-shuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-er","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-076X","authenticated-orcid":false,"given":"Sheng-an","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"8705_CR1","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. 2021;21:298\u2013312.","journal-title":"Nat Rev Cancer"},{"key":"8705_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.coi.2019.12.005","volume":"64","author":"JD Colbert","year":"2020","unstructured":"Colbert JD, Cruz FM, Rock KL. Cross-presentation of exogenous antigens on MHC I molecules. Curr Opin Immunol. 2020;64:1\u20138.","journal-title":"Curr Opin Immunol"},{"key":"8705_CR3","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/14058","volume":"1","author":"A Rodriguez","year":"1999","unstructured":"Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol. 1999;1:362\u20138.","journal-title":"Nat Cell Biol"},{"key":"8705_CR4","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0092-8674(00)00038-6","volume":"102","author":"WS Garrett","year":"2000","unstructured":"Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, Developmental control of endocytosis in dendritic cells by Cdc42. Cell. 2000;102:325\u201334.","journal-title":"Cell"},{"key":"8705_CR5","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.immuni.2012.03.009","volume":"36","author":"JG Zhang","year":"2012","unstructured":"Zhang JG, Czabotar PE, Policheni AN, Caminschi I, Wan SS, Kitsoulis S, et al. The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity. 2012;36:646\u201357.","journal-title":"Immunity"},{"key":"8705_CR6","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s12026-012-8300-z","volume":"53","author":"RA Hopkins","year":"2012","unstructured":"Hopkins RA, Connolly JE. The specialized roles of immature and mature dendritic cells in antigen cross-presentation. Immunol Res. 2012;53:91\u2013107.","journal-title":"Immunol Res"},{"key":"8705_CR7","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.immuni.2004.07.004","volume":"21","author":"L Shen","year":"2004","unstructured":"Shen L, Sigal LJ, Boes M, Rock KL. Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity. 2004;21:155\u201365.","journal-title":"Immunity"},{"key":"8705_CR8","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.cell.2006.05.035","volume":"126","author":"A Savina","year":"2006","unstructured":"Savina A, Jancic C, Hugues S, Guermonprez P, Vargas P, Moura IC, et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell. 2006;126:205\u201318.","journal-title":"Cell"},{"key":"8705_CR9","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.immuni.2015.04.008","volume":"42","author":"M Zehner","year":"2015","unstructured":"Zehner M, Marschall AL, Bos E, Schloetel JG, Kreer C, Fehrenschild D, et al. The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells. Immunity. 2015;42:850\u201363.","journal-title":"Immunity"},{"key":"8705_CR10","doi-asserted-by":"publisher","first-page":"6229","DOI":"10.1007\/s00018-021-03914-7","volume":"78","author":"M Kulma","year":"2021","unstructured":"Kulma M, Anderluh G. Beyond pore formation: reorganization of the plasma membrane induced by pore-forming proteins. Cell Mol Life Sci. 2021;78:6229\u201349.","journal-title":"Cell Mol Life Sci"},{"key":"8705_CR11","doi-asserted-by":"publisher","first-page":"6702","DOI":"10.1073\/pnas.1321317111","volume":"111","author":"Y Xiang","year":"2014","unstructured":"Xiang Y, Yan C, Guo X, Zhou K, Li S, Gao Q, et al. Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection. Proc Natl Acad Sci USA. 2014;111:6702\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8705_CR12","doi-asserted-by":"crossref","unstructured":"Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science 2020;368:7548.","DOI":"10.1126\/science.aaz7548"},{"key":"8705_CR13","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nri3839","volume":"15","author":"I Voskoboinik","year":"2015","unstructured":"Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388\u2013400.","journal-title":"Nat Rev Immunol"},{"key":"8705_CR14","doi-asserted-by":"publisher","first-page":"2772","DOI":"10.4049\/jimmunol.1600310","volume":"198","author":"RJ Laborde","year":"2017","unstructured":"Laborde RJ, Sanchez-Ferras O, Luzardo MC, Cruz-Leal Y, Fernandez A, Mesa C, et al. Novel adjuvant based on the pore-forming protein sticholysin II encapsulated into liposomes effectively enhances the antigen-specific CTL-mediated immune response. J Immunol. 2017;198:2772\u201384.","journal-title":"J Immunol"},{"key":"8705_CR15","doi-asserted-by":"crossref","unstructured":"Gonzales GA, Huang S, Wilkinson L, Nguyen JA, Sikdar S, Piot C, et al. The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells. Sci Immunol. 2024;9:2168.","DOI":"10.1126\/sciimmunol.adn2168"},{"key":"8705_CR16","doi-asserted-by":"publisher","first-page":"13609","DOI":"10.1096\/fj.202001176R","volume":"34","author":"CJ Deng","year":"2020","unstructured":"Deng CJ, Liu L, Liu LZ, Wang QQ, Guo XL, Lee WH, et al. A secreted pore-forming protein modulates cellular endolysosomes to augment antigen presentation. FASEB J. 2020;34:13609\u201325.","journal-title":"FASEB J"},{"key":"8705_CR17","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1093\/infdis\/jix183","volume":"215","author":"SA Li","year":"2017","unstructured":"Li SA, Liu L, Guo XL, Zhang YY, Xiang Y, Wang QQ, et al. Host pore-forming protein complex neutralizes the acidification of endocytic organelles to counteract intracellular pathogens. J Infect Dis. 2017;215:1753\u201363.","journal-title":"J Infect Dis"},{"key":"8705_CR18","doi-asserted-by":"crossref","unstructured":"Bayly-Jones C, Pang SS, Spicer BA, Whisstock JC, Dunstone MA. Ancient but not forgotten: new insights into MPEG1, a macrophage perforin-like immune effector. Front Immunol. 2020;11:581906.","DOI":"10.3389\/fimmu.2020.581906"},{"key":"8705_CR19","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1182\/blood.V85.6.1620.bloodjournal8561620","volume":"85","author":"K Spilsbury","year":"1995","unstructured":"Spilsbury K, O\u2019Mara MA, Wu WM, Rowe PB, Symonds G, Takayama Y. Isolation of a novel macrophage-specific gene by differential cDNA analysis. Blood. 1995;85:1620\u20139.","journal-title":"Blood"},{"key":"8705_CR20","doi-asserted-by":"crossref","unstructured":"McCormack RM, de Armas LR, Shiratsuchi M, Fiorentino DG, Olsson ML, Lichtenheld MG, et al. Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. Elife. 2015;4:e06508.","DOI":"10.7554\/eLife.06508"},{"key":"8705_CR21","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1128\/IAI.01434-15","volume":"84","author":"R McCormack","year":"2016","unstructured":"McCormack R, Bahnan W, Shrestha N, Boucher J, Barreto M, Barrera CM, et al. Perforin-2 protects host cells and mice by restricting the vacuole to cytosol transitioning of a bacterial pathogen. Infect Immun. 2016;84:1083\u201391.","journal-title":"Infect Immun"},{"key":"8705_CR22","doi-asserted-by":"crossref","unstructured":"Hung LY, Tanaka Y, Herbine K, Pastore C, Singh B, Ferguson A, et al. Cellular context of IL-33 expression dictates impact on anti-helminth immunity. Sci Immunol. 2020;5:eabc6259.","DOI":"10.1126\/sciimmunol.abc6259"},{"key":"8705_CR23","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1111\/imcb.12554","volume":"100","author":"S Ebrahimnezhaddarzi","year":"2022","unstructured":"Ebrahimnezhaddarzi S, Bird CH, Allison CC, Tuipulotu DE, Kostoulias X, Macri C, et al. Mpeg1 is not essential for antibacterial or antiviral immunity, but is implicated in antigen presentation. Immunol Cell Biol. 2022;100:529\u201346.","journal-title":"Immunol Cell Biol"},{"key":"8705_CR24","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1126\/science.adg8802","volume":"380","author":"P Rodriguez-Silvestre","year":"2023","unstructured":"Rodriguez-Silvestre P, Laub M, Krawczyk PA, Davies AK, Schessner JP, Parveen R, et al. Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells. Science. 2023;380:1258\u201365.","journal-title":"Science"},{"key":"8705_CR25","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/j.immuni.2015.05.018","volume":"42","author":"J Helft","year":"2015","unstructured":"Helft J, Bottcher J, Chakravarty P, Zelenay S, Huotari J, Schraml BU, et al. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c(+)MHCII(+) macrophages and dendritic cells. Immunity. 2015;42:1197\u2013211.","journal-title":"Immunity"},{"key":"8705_CR26","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1182\/blood-2013-12-545772","volume":"124","author":"CT Mayer","year":"2014","unstructured":"Mayer CT, Ghorbani P, Nandan A, Dudek M, Arnold-Schrauf C, Hesse C, et al. Selective and efficient generation of functional Batf3-dependent CD103+ dendritic cells from mouse bone marrow. Blood. 2014;124:3081\u201391.","journal-title":"Blood"},{"key":"8705_CR27","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S1074-7613(00)80255-1","volume":"5","author":"M Jondal","year":"1996","unstructured":"Jondal M, Schirmbeck R, Reimann J. MHC class I-restricted CTL responses to exogenous antigens. Immunity. 1996;5:295\u2013302.","journal-title":"Immunity"},{"key":"8705_CR28","doi-asserted-by":"publisher","first-page":"129","DOI":"10.4049\/jimmunol.0804260","volume":"183","author":"L Klotz","year":"2009","unstructured":"Klotz L, Hucke S, Thimm D, Classen S, Gaarz A, Schultze J, et al. Increased antigen cross-presentation but impaired cross-priming after activation of peroxisome proliferator-activated receptor gamma is mediated by up-regulation of B7H1. J Immunol. 2009;183:129\u201336.","journal-title":"J Immunol"},{"key":"8705_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60922-y","volume":"16","author":"X Ju","year":"2025","unstructured":"Ju X, Putz EM, Liu Y, Yuan D, Sun G, Koda S, et al. Metabotropic glutamate receptor 4-mediated glutamatfergic signaling reshapes the tumor microenvironment by regulating dendritic cell maturation. Nat Commun. 2025;16:5874.","journal-title":"Nat Commun"},{"key":"8705_CR30","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1038\/sj.gt.3300747","volume":"5","author":"BE Souberbielle","year":"1998","unstructured":"Souberbielle BE, Westby M, Ganz S, Kayaga J, Mendes R, Morrow WJ, et al. Comparison of four strategies for tumour vaccination in the B16-F10 melanoma model. Gene Ther. 1998;5:1447\u201354.","journal-title":"Gene Ther"},{"key":"8705_CR31","doi-asserted-by":"publisher","first-page":"4287","DOI":"10.1073\/pnas.0910609107","volume":"107","author":"CD Platt","year":"2010","unstructured":"Platt CD, Ma JK, Chalouni C, Ebersold M, Bou-Reslan H, Carano RA, et al. Mature dendritic cells use endocytic receptors to capture and present antigens. Proc Natl Acad Sci USA. 2010;107:4287\u201392.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8705_CR32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41551-024-01178-7","volume":"8","author":"Q Feng","year":"2024","unstructured":"Feng Q, Bennett Z, Grichuk A, Pantoja R, Huang T, Faubert B, et al. Severely polarized extracellular acidity around tumour cells. Nat Biomed Eng. 2024;8:787\u201399.","journal-title":"Nat Biomed Eng"},{"key":"8705_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12279-2","volume":"10","author":"SS Pang","year":"2019","unstructured":"Pang SS, Bayly-Jones C, Radjainia M, Spicer BA, Law R, Hodel AW, et al. The cryo-EM structure of the acid activatable pore-forming immune effector macrophage-expressed gene 1. Nat Commun. 2019;10:4288.","journal-title":"Nat Commun"},{"key":"8705_CR34","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/ni.2050","volume":"12","author":"J Thiery","year":"2011","unstructured":"Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, et al. Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells. Nat Immunol. 2011;12:770\u20137.","journal-title":"Nat Immunol"},{"key":"8705_CR35","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.immuni.2005.08.001","volume":"23","author":"D Keefe","year":"2005","unstructured":"Keefe D, Shi L, Feske S, Massol R, Navarro F, Kirchhausen T, et al. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity. 2005;23:249\u201362.","journal-title":"Immunity"},{"key":"8705_CR36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247136","volume":"343","author":"AJ Jimenez","year":"2014","unstructured":"Jimenez AJ, Maiuri P, Lafaurie-Janvore J, Divoux S, Piel M, Perez F. ESCRT machinery is required for plasma membrane repair. Science. 2014;343:1247136.","journal-title":"Science"},{"key":"8705_CR37","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.3389\/fimmu.2018.01643","volume":"9","author":"M Embgenbroich","year":"2018","unstructured":"Embgenbroich M, Burgdorf S. Current concepts of antigen cross-presentation. Front Immunol. 2018;9:1643.","journal-title":"Front Immunol"},{"key":"8705_CR38","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1093\/jleuko\/qiad117","volume":"114","author":"J Yang","year":"2023","unstructured":"Yang J, Rong SJ, Zhou HF, Yang C, Sun F, Li JY. Lysosomal control of dendritic cell function. J Leukoc Biol. 2023;114:518\u201331.","journal-title":"J Leukoc Biol"},{"key":"8705_CR39","doi-asserted-by":"crossref","unstructured":"Cruz-Leal Y, Grubaugh D, Nogueira CV, Lopetegui-Gonz\u00e1lez I, Del Valle A, Escalona F, et al. The vacuolar pathway in macrophages plays a major role in antigen cross-presentation induced by the pore-forming protein sticholysin II encapsulated into liposomes. Front Immunol. 2018;9:2473.","DOI":"10.3389\/fimmu.2018.02473"},{"key":"8705_CR40","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1126\/science.1137971","volume":"316","author":"S Burgdorf","year":"2007","unstructured":"Burgdorf S, Kautz A, Bohnert V, Knolle PA, Kurts C. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science. 2007;316:612\u20136.","journal-title":"Science"},{"key":"8705_CR41","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1084\/jem.188.2.409","volume":"188","author":"C Kurts","year":"1998","unstructured":"Kurts C, Miller JF, Subramaniam RM, Carbone FR, Heath WR. Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction. J Exp Med. 1998;188:409\u201314.","journal-title":"J Exp Med"},{"key":"8705_CR42","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.4049\/jimmunol.170.8.4102","volume":"170","author":"SK Datta","year":"2003","unstructured":"Datta SK, Redecke V, Prilliman KR, Takabayashi K, Corr M, Tallant T, et al. A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. J Immunol. 2003;170:4102\u201310.","journal-title":"J Immunol"},{"key":"8705_CR43","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/ni.1601","volume":"9","author":"S Burgdorf","year":"2008","unstructured":"Burgdorf S, Sch\u00f6lz C, Kautz A, Tamp\u00e9 R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008;9:558\u201366.","journal-title":"Nat Immunol"},{"key":"8705_CR44","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.immuni.2008.04.010","volume":"28","author":"JJ Obar","year":"2008","unstructured":"Obar JJ, Khanna KM, Lefrancois L. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity. 2008;28:859\u201369.","journal-title":"Immunity"},{"key":"8705_CR45","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1673125","volume":"9","author":"BJ Hos","year":"2019","unstructured":"Hos BJ, Camps M, van den Bulk J, Tondini E, van den Ende TC, Ruano D, et al. Identification of a neo-epitope dominating endogenous CD8 T cell responses to MC-38 colorectal cancer. Oncoimmunology. 2019;9:1673125.","journal-title":"Oncoimmunology"},{"key":"8705_CR46","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1073\/pnas.0712394105","volume":"105","author":"ML Lin","year":"2008","unstructured":"Lin ML, Zhan Y, Proietto AI, Prato S, Wu L, Heath WR, et al. Selective suicide of cross-presenting CD8+ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset. Proc Natl Acad Sci USA. 2008;105:3029\u201334.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8705_CR47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238484","volume":"15","author":"SC Nalle","year":"2020","unstructured":"Nalle SC, Barreira DSR, Zhang H, Decker M, Chalouni C, Xu M, et al. Aquaporin-3 regulates endosome-to-cytosol transfer via lipid peroxidation for cross presentation. PLoS ONE. 2020;15:e238484.","journal-title":"PLoS ONE"},{"key":"8705_CR48","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.4049\/jimmunol.1004163","volume":"186","author":"S Lorenzi","year":"2011","unstructured":"Lorenzi S, Mattei F, Sistigu A, Bracci L, Spadaro F, Sanchez M, et al. Type I IFNs control antigen retention and survival of CD8alpha(+) dendritic cells after uptake of tumor apoptotic cells leading to cross-priming. J Immunol. 2011;186:5142\u201350.","journal-title":"J Immunol"},{"key":"8705_CR49","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/nature08511","volume":"462","author":"Y Nakanishi","year":"2009","unstructured":"Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature. 2009;462:510\u20133.","journal-title":"Nature"},{"key":"8705_CR50","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/ni.2079","volume":"12","author":"S Feau","year":"2011","unstructured":"Feau S, Arens R, Togher S, Schoenberger SP. Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells. Nat Immunol. 2011;12:908\u201313.","journal-title":"Nat Immunol"},{"key":"8705_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6646","volume":"5","author":"LL Scheffer","year":"2014","unstructured":"Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, et al. Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair. Nat Commun. 2014;5:5646.","journal-title":"Nat Commun"},{"key":"8705_CR52","doi-asserted-by":"publisher","first-page":"R392","DOI":"10.1016\/j.cub.2017.12.034","volume":"28","author":"NW Andrews","year":"2018","unstructured":"Andrews NW, Corrotte M. Plasma membrane repair. Curr Biol. 2018;28:R392\u2013R397.","journal-title":"Curr Biol"},{"key":"8705_CR53","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1083\/jcb.201003053","volume":"189","author":"C Tam","year":"2010","unstructured":"Tam C, Idone V, Devlin C, Fernandes MC, Flannery A, He X, et al. Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. J Cell Biol. 2010;189:1027\u201338.","journal-title":"J Cell Biol"},{"key":"8705_CR54","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.4049\/jimmunol.172.5.3196","volume":"172","author":"M Vermeulen","year":"2004","unstructured":"Vermeulen M, Giordano M, Trevani AS, Sedlik C, Gamberale R, Fernandez-Calotti P, et al. Acidosis improves uptake of antigens and MHC class I-restricted presentation by dendritic cells. J Immunol. 2004;172:3196\u2013204.","journal-title":"J Immunol"},{"key":"8705_CR55","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41590-019-0313-5","volume":"20","author":"Z Erlich","year":"2019","unstructured":"Erlich Z, Shlomovitz I, Edry-Botzer L, Cohen H, Frank D, Wang H, et al. Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model. Nat Immunol. 2019;20:397\u2013406.","journal-title":"Nat Immunol"},{"key":"8705_CR56","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.4049\/jimmunol.166.10.6099","volume":"166","author":"M Li","year":"2001","unstructured":"Li M, Davey GM, Sutherland RM, Kurts C, Lew AM, Hirst C, et al. Cell-associated ovalbumin is cross-presented much more efficiently than soluble ovalbumin in vivo1. J Immunol. 2001;166:6099\u2013103.","journal-title":"J Immunol"},{"key":"8705_CR57","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1084\/jem.20170229","volume":"214","author":"A Alloatti","year":"2017","unstructured":"Alloatti A, Rookhuizen DC, Joannas L, Carpier JM, Iborra S, Magalhaes JG, et al. Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity. J Exp Med. 2017;214:2231\u201341.","journal-title":"J Exp Med"},{"key":"8705_CR58","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.4049\/jimmunol.2001426","volume":"207","author":"KR Wilson","year":"2021","unstructured":"Wilson KR, Jenika D, Blum AB, Macri C, Xu B, Liu H, et al. MHC class II ubiquitination regulates dendritic cell function and immunity. J Immunol. 2021;207:2255\u201364.","journal-title":"J Immunol"},{"key":"8705_CR59","doi-asserted-by":"publisher","first-page":"4016","DOI":"10.1016\/j.cell.2021.05.021","volume":"184","author":"E Giampazolias","year":"2021","unstructured":"Giampazolias E, Schulz O, Lim K, Rogers NC, Chakravarty P, Srinivasan N, et al. Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity. Cell. 2021;184:4016\u201331.","journal-title":"Cell"},{"key":"8705_CR60","doi-asserted-by":"publisher","first-page":"6770","DOI":"10.4049\/jimmunol.176.11.6770","volume":"176","author":"S Burgdorf","year":"2006","unstructured":"Burgdorf S, Lukacs-Kornek V, Kurts C. The Mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation1. J Immunol. 2006;176:6770\u20136.","journal-title":"J Immunol"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08705-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08705-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08705-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:03:51Z","timestamp":1779210231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08705-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8705"],"URL":"https:\/\/doi.org\/10.1038\/s41419-026-08705-1","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"We confirm that all experiments were conducted in accordance with relevant guidelines and regulations and have been approved by the Animal Care and Use Committee of Kunming Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}],"article-number":"485"}}