Science Translational Medicine最新文献

{"title":"Tissue-resident memory CD4+ T cells infiltrate the CNS in progressive multiple sclerosis and contribute to chronic autoimmunity in mice","authors":"Aurora Pignata,&nbsp;David Frieser,&nbsp;Carmen Gonzalez-Fierro,&nbsp;Cheng-Chih Hsiao,&nbsp;Hendrik J. Engelenburg,&nbsp;Marine Alis,&nbsp;Ilan Fijalkow,&nbsp;Vincent Cazaentre,&nbsp;Lucie Nozeran,&nbsp;Romain Miranda-Capet,&nbsp;Eloïse Dufourd,&nbsp;Thaïs Vermeulen,&nbsp;Amel Aïda,&nbsp;Carole Le Coz,&nbsp;Klaas Van Gisbergen,&nbsp;Nicolas Blanchard,&nbsp;Jörg Hamann,&nbsp;Joost Smolders,&nbsp;Roland S. Liblau,&nbsp;Frederick Masson","doi":"10.1126/scitranslmed.adp8109","DOIUrl":"10.1126/scitranslmed.adp8109","url":null,"abstract":"<div >Preventing T cell migration to the central nervous system (CNS) has remarkable therapeutic effects in relapsing-remitting multiple sclerosis (RRMS) but is poorly effective against the progressive form (PMS). Disability progression in PMS likely results from an interplay between smoldering local inflammation and neurodegeneration. The mechanisms sustaining the chronicity of PMS are poorly understood. Here, we investigated the potential role of tissue-resident memory CD4⁺ T cells (CD4⁺ Trm cells) in sustaining chronic CNS autoimmunity. We showed that CD4⁺ Trm cells were present in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in brain tissues from persons with PMS. Using flow cytometry and immunohistofluorescence analysis, we revealed the presence of bona fide CD4⁺ Trm cells expressing characteristic Trm cell surface markers, including CD69, CXCR6, P2RX7, and CD49a, in the CNS of mice with EAE and in the brains of persons with PMS. These T cells also expressed the transcription factor Hobit in mice with chronic EAE. Single-cell transcriptomic analysis uncovered the transcriptional heterogeneity and inflammatory potential of CD4⁺ Trm cells, and, accordingly, these cells localized within CNS inflammatory lesions of mice with EAE and persons with PMS. Last, either genetic or pharmacological depletion of CD4⁺ Trm cells combined with antibody-mediated depletion of the recirculating CD4⁺ T cell compartment alleviated neurological signs during the chronic phase of EAE. Our results indicate that CD4⁺ Trm cells contribute to maintain a chronic inflammatory state in the CNS and suggest that therapeutic strategies for PMS should consider targeting the CNS-resident T cell compartment.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 808","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective envelope dimer epitope–like antibodies are elicited against dengue virus in children after infection and vaccination","authors":"Patrick I. Mpingabo,&nbsp;Michelle Ylade,&nbsp;Rosemary A. Aogo,&nbsp;Maria Vinna Crisostomo,&nbsp;Devina J. Thiono,&nbsp;Jedas Veronica Daag,&nbsp;Kristal-An Agrupis,&nbsp;Ana Coello Escoto,&nbsp;Guillermo L. Raimundi-Rodriguez,&nbsp;Camila D. Odio,&nbsp;Maria Abad Fernandez,&nbsp;Laura White,&nbsp;Aravinda M. de Silva,&nbsp;Jacqueline Deen,&nbsp;Leah C. Katzelnick","doi":"10.1126/scitranslmed.adq0571","DOIUrl":"10.1126/scitranslmed.adq0571","url":null,"abstract":"<div >Cross-reactive antibodies to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue virus (DENV) infection and disease. Here, we measured antibodies targeting a quaternary epitope called the envelope dimer epitope (EDE) as well as neutralizing and binding antibodies and evaluated their association with DENV infection, vaccine response, and disease outcome in dengue-vaccinated (<i>n</i> = 164) and dengue-unvaccinated children (<i>n</i> = 88) within a longitudinal cohort in Cebu, Philippines (<i>n</i> = 2996). Antibodies targeting EDE were prevalent and associated with broad neutralization of mature DENV1 to DENV4 virions in those with evidence of at least two prior DENV infections but were mostly absent in those with only one prior infection. Subsequent infection and vaccination boosted titers of EDE-like antibodies, neutralizing antibodies, and DENV-binding antibodies. EDE-like antibodies were associated with reduced risk of symptomatic dengue and more severe dengue and statistically explained the protective effect of binding and neutralizing antibodies on dengue. Thus, antibodies targeting quaternary epitopes help explain the broad cross-protection observed in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 808","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for the Research Article “Combining a CAR and a chimeric costimulatory receptor enhances T cell sensitivity to low antigen density and promotes persistence” by A. Katsarou et al.","authors":"","doi":"10.1126/scitranslmed.aea1242","DOIUrl":"10.1126/scitranslmed.aea1242","url":null,"abstract":"","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 808","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer","authors":"Elias Quijano,&nbsp;Diana Martinez-Saucedo,&nbsp;Zaira Ianniello,&nbsp;Natasha Pinto-Medici,&nbsp;Madison Rackear,&nbsp;Haoting Chen,&nbsp;Luiz Lola-Pereira,&nbsp;Yanfeng Liu,&nbsp;Denise Hegan,&nbsp;Xinning Shan,&nbsp;Robert Tseng,&nbsp;Deanne Yugawa,&nbsp;Sumedha Chowdhury,&nbsp;Minsoo Khang,&nbsp;Jay P. Singh,&nbsp;Rashed Abdullah,&nbsp;Perisa Azhir,&nbsp;Soki Kashima,&nbsp;Wendy S. Woods,&nbsp;Nicholas Gosstola,&nbsp;Bruce C. Turner,&nbsp;Stephen Squinto,&nbsp;Dale L. Ludwig,&nbsp;Ranjit S. Bindra,&nbsp;Marie E. Robert,&nbsp;David A. Braun,&nbsp;Pablo Perez Pinera,&nbsp;W. Mark Saltzman,&nbsp;Luisa F. Escobar-Hoyos,&nbsp;Peter M. Glazer","doi":"10.1126/scitranslmed.adk1868","DOIUrl":"10.1126/scitranslmed.adk1868","url":null,"abstract":"<div >There is intense interest in the advancement of RNAs as rationally designed therapeutic agents, especially in oncology, where a major focus is to use RNAs to stimulate pattern recognition receptors to leverage innate immune responses. However, the inability to selectively deliver therapeutic RNAs within target cells after intravenous administration now hinders the development of this type of treatment for cancer and other disorders. Here, we found that a tumor-targeting, cell-penetrating, and RNA binding monoclonal antibody, TMAB3, can form stable, noncovalent antibody/RNA complexes of a discrete size that mediate highly specific and functional delivery of RNAs into tumors. Using 3p-hpRNA, an agonist of the pattern recognition receptor retinoic acid–inducible gene-I (RIG-I), we observed robust antitumor efficacy of systemically administered TMAB3/3p-hpRNA complexes in mouse models of pancreatic cancer, medulloblastoma, and melanoma. In the KPC syngeneic, orthotopic pancreatic cancer model in immunocompetent mice, treatment with TMAB3/3p-hpRNA tripled animal survival, decreased tumor growth, and specifically targeted malignant cells, with a 1500-fold difference in RNA delivery into tumor cells versus nonmalignant cells within the tumor mass. Single-cell RNA sequencing (scRNA-seq) and flow cytometry demonstrated that TMAB3/3p-hpRNA treatment elicited a potent antitumoral immune response characterized by RIG-I activation and increased infiltration and activity of cytotoxic T cells. These studies established that TMAB3/RNA complexes can deliver RNA payloads specifically to hard-to-treat tumor cells to achieve antitumor efficacy, providing an antibody-based platform to advance the study of RNA therapies for the treatment of patients with cancer.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of liquid mRNA therapeutics by an engineered capsule for treatment of preclinical intestinal disease","authors":"Xiangang Huang,&nbsp;Chuang Liu,&nbsp;Shonit Nair Sharma,&nbsp;Xinru You,&nbsp;Shuying Chen,&nbsp;Yongjiang Li,&nbsp;Hai-Jun Liu,&nbsp;Bin Liu,&nbsp;Qimanguli Saiding,&nbsp;Wei Chen,&nbsp;Yuhan Lee,&nbsp;Na Kong,&nbsp;Reza Abdi,&nbsp;Wei Tao","doi":"10.1126/scitranslmed.adu1493","DOIUrl":"10.1126/scitranslmed.adu1493","url":null,"abstract":"<div >Oral delivery of messenger RNA (mRNA) therapeutics could offer noninvasive and self-administered treatments and vaccinations. However, the development of oral mRNA therapeutics remains challenging because of the degradative conditions of the gastrointestinal (GI) tract. Here, we engineered a capsule-based device, named RNACap, designed for oral delivery of liquid mRNA nanoparticle (NP) therapeutics to the intestines. RNACap protects mRNA from the acidic stomach environment while allowing rapid release into the intestines in response to intestinal neutral pH, pressure release due to the dissolution of capsule cap, and natural intestinal contractions (peristalsis). This process enables NP-mediated delivery of mRNA into intestinal cells for in vivo transfection. We optimized an NP formulation for rapid intestinal mRNA delivery. In rat and porcine models, we confirmed that the RNACap remains intact in the stomach but releases its contents within the intestines. The release of mRNA NPs led to the expression of multiple mRNAs. The therapeutic effect of the RNACap was demonstrated by acute and delayed treatment in two rat colitis models. Orally administered RNACaps loaded with mRNA encoding interleukin-10 (<i>IL-10</i> mRNA NP) reduced proinflammatory cytokine concentrations in both blood and tissues, ultimately alleviating colitis. Furthermore, using a large-animal model of swine, we showed that RNACaps remained intact in the stomach, disassembled in the intestine, and resulted in robust mRNA expression just 8.5 hours after administration. RNACap represents a promising platform for the oral delivery of liquid mRNA therapeutics to the GI tract for treating challenging intestinal diseases and potentially other conditions.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-recipient mismatch at the SIRPA locus adversely affects kidney allograft outcomes","authors":"Daqiang Zhao,&nbsp;Hehua Dai,&nbsp;Camila Macedo,&nbsp;Steven M. Sanders,&nbsp;Charbel Elias,&nbsp;Andrew J. Friday,&nbsp;Mohamad Zaidan,&nbsp;Amanda L. Williams,&nbsp;Beth D. Elinoff,&nbsp;Martin H. Oberbarnscheidt,&nbsp;Jayne Danska,&nbsp;Adriana Zeevi,&nbsp;Parmjeet Randhawa,&nbsp;Amit D. Tevar,&nbsp;Sundaram Hariharan,&nbsp;David M. Rothstein,&nbsp;Khodor I. Abou-Daya,&nbsp;Aleksandar Senev,&nbsp;Anat R. Tambur,&nbsp;Diana Metes,&nbsp;Olivier Thaunat,&nbsp;Fadi G. Lakkis,&nbsp;Aravind Cherukuri","doi":"10.1126/scitranslmed.ady1135","DOIUrl":"10.1126/scitranslmed.ady1135","url":null,"abstract":"<div >Donor-recipient mismatches in histocompatibility antigens recognized by lymphoid cells have been demonstrated to adversely affect allograft outcomes. In contrast, it remains unclear whether mismatches sensed by innate myeloid cells have a similar effect. We investigated the consequences of mismatch in the polymorphic gene encoding signal regulatory protein α (SIRPα) on kidney allograft pathology and survival in mice and humans. We found that SIRPα variants elicit monocyte activation by binding to CD47 and that eliminating SIRPα mismatch or recipient CD47 expression prevented chronic allograft pathology in mice receiving major histocompatibility complex (MHC)–mismatched renal allografts. Human genomic analysis identified two haplotype categories, A and B, encoding SIRPα variants with distinct CD47 binding interfaces. In kidney transplant recipients (<i>N</i> = 455), SIRPα mismatch was associated with increased acute rejection and graft fibrosis in the first posttransplant year, and A recipients of B kidneys had reduced long-term graft survival (hazard ratio, 3.2; 95% confidence interval, 1.5 to 6.9; <i>P</i> = 0.002), a finding that was confirmed in an independent validation cohort (<i>N</i> = 258). Moreover, monocytes in these graft recipients had an activated phenotype. The effects of SIRPα mismatch were independent of ancestry, human leukocyte antigen mismatch, donor-specific antibodies, and delayed graft function. Therefore, these data demonstrate that a donor-recipient mismatch that causes innate immune activation is a determinant of kidney transplantation outcomes.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A8/A9 perturbation in bone marrow blunts antitumor immunity by promoting protumorigenic myelopoiesis in mouse models","authors":"Wen Luo,&nbsp;Xingxing Su,&nbsp;Qiao Zhang,&nbsp;Zhongyu Wang,&nbsp;Zheng Jin,&nbsp;Yanan Li,&nbsp;Yang Fei,&nbsp;Dong Zeng,&nbsp;Xianghua Zeng,&nbsp;Guitong Lv,&nbsp;Mengyi Li,&nbsp;Jiani Huang,&nbsp;Haoran Zha,&nbsp;Ji Liu,&nbsp;Zhong Luo,&nbsp;Haixia Long,&nbsp;Bo Zhu","doi":"10.1126/scitranslmed.adr3963","DOIUrl":"10.1126/scitranslmed.adr3963","url":null,"abstract":"<div >S100A8/A9 plays a critical role in the formation of an immunosuppressive tumor microenvironment. Therefore, it is important to identify inhibitors targeting S100A8/A9 to enhance antitumor immunity. However, systemic targeting of S100A8/A9 in clinical trials has shown minimal effects. Understanding the reasons underlying this underperformance is important for developing drugs targeting S100A8/A9 that could effectively reverse the immunosuppressive tumor microenvironment. In this study, using hematopoietic system–specific conditional knockout mice in heterotopic models of lung and colon cancer and systemic pharmacological interference, we demonstrated that S100A8/A9 perturbation in the hematopoietic system accelerates tumor progression by attenuating T cell–mediated antitumor immunity. Mechanistically, S100A8/A9 perturbation triggered myeloid-biased differentiation in the bone marrow by promoting the production of abnormal granulocyte-monocyte progenitors. The local release of S100A8/A9 inhibitors using a tumor-targeted drug delivery system exhibited antitumor potential by avoiding myelopoiesis-promoting effects. These findings reveal a mechanism underlying the limited efficacy of systemic S100A8/A9 inhibition and propose a targeted strategy to enhance antitumor effects.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scitranslmed.adr3963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SIRT2 induces MLH1 deficiency and boosts antitumor immunity in preclinical colorectal cancer models","authors":"Qianling Gao,&nbsp;Lanlan Yang,&nbsp;Shubiao Ye,&nbsp;Mingru Mai,&nbsp;Yiting Liu,&nbsp;Xuefei Jiang,&nbsp;Xingzhi Feng,&nbsp;Zihuan Yang","doi":"10.1126/scitranslmed.adv0766","DOIUrl":"10.1126/scitranslmed.adv0766","url":null,"abstract":"<div >Low tumor mutation burden and an immunosuppressive tumor microenvironment (TME) of colorectal cancers (CRCs) contribute to resistance to immune-checkpoint inhibitors in patients. Understanding the mechanisms of cancer immune evasion will be helpful to develop new therapeutic strategies. Here, leveraging mass spectrometry–based proteomic profiling data and clinical validation, we identified that low sirtuin 2 (SIRT2) expression was associated with improved prognosis and an immune-active TME in CRC. Specifically, genetic knockdown or pharmacological inhibition of SIRT2 resulted in enhanced infiltration and cytotoxicity of CD8⁺ T cells, leading to tumor regression across multiple CRC mouse models and patient-derived organoids. Further in vitro experimental analysis demonstrated that SIRT2 interacted with and deacetylated MutL protein homolog 1 (MLH1) at Lys^402/443/461, thereby preventing MLH1 ubiquitination and degradation. SIRT2 knockdown or inhibition down-regulated MLH1, increasing DNA damage and activating the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway. In addition, both in vivo and in vitro experiments indicated that SIRT2 inhibition stimulated the production of tumor neoantigens and enhanced major histocompatibility complex class I (MHC-I) expression, reprogramming the TME toward an immune-active status and inducing long-lasting immune memory. Last, a combination strategy using SIRT2 inhibitor 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2) and anti–programmed cell death protein–1 (PD-1) therapy enhanced immune response, making tumors susceptible to immunotherapy and driving substantial tumor regression in vivo. Our study uncovers a role of SIRT2 in reprogramming TME and underscores the potential of targeting SIRT2 to sensitize CRC to immunotherapy.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target","authors":"Satheesh Chonat,&nbsp;Jayre A. Jones,&nbsp;Seema R. Patel,&nbsp;William M. Briones,&nbsp;Michelle L. Schoettler,&nbsp;Maya Maarouf,&nbsp;Lauren A. Jeffers,&nbsp;Olufolake Adisa,&nbsp;Fang Tan,&nbsp;Earl Fields,&nbsp;Morgan S. Sterling,&nbsp;Ryan P. Jajosky,&nbsp;Hans Verkerke,&nbsp;Sara H. Graciaa,&nbsp;Elisabetta M. Foppiani,&nbsp;Ross M. Fasano,&nbsp;Patricia E. Zerra,&nbsp;Yongzhi Qiu,&nbsp;Connie M. Arthur,&nbsp;Wilbur A. Lam,&nbsp;Solomon F. Ofori-Acquah,&nbsp;Michael Koval,&nbsp;Clinton H. Joiner,&nbsp;David R. Archer,&nbsp;Sean R. Stowell","doi":"10.1126/scitranslmed.adl4922","DOIUrl":"10.1126/scitranslmed.adl4922","url":null,"abstract":"<div >Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for the Research Article “Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer” by J. Li et al.","authors":"","doi":"10.1126/scitranslmed.aea0591","DOIUrl":"10.1126/scitranslmed.aea0591","url":null,"abstract":"","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}