{"title":"PerioAI: A digital system for periodontal disease diagnosis from an intra-oral scan and cone-beam CT image.","authors":"Minhui Tan, Zhiming Cui, Yuan Li, Yu Fang, Lanzhuju Mei, Yue Zhao, Xinyu Wu, Hongchang Lai, Maurizio S Tonetti, Dinggang Shen","doi":"10.1016/j.xcrm.2025.102186","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102186","url":null,"abstract":"<p><p>Periodontal disease diagnosis and treatment planning are critical for preventing bone and tooth loss. Clinically, dentists manually measure periodontal pocket depth with probes while integrating bone structure from imaging to assess periodontal status, a process that is subjective, invasive, and cognitively burdensome. Here, we propose PerioAI, an accurate, automatic, and non-invasive system that directly measures the gingiva-bone distance (GBD) and provides soft and hard tissue information digitally. PerioAI is a full-stack process comprising four key components: intra-oral scan (IOS) segmentation, cone-beam computed tomography (CBCT) image segmentation, multimodal data fusion, and digital probing measurement. We evaluated PerioAI on multicenter cohorts comprising 2,507 patients. Outstanding IOS and CBCT segmentation performances ensure accuracy throughout the full-stack process. Moreover, digital probing achieves remarkable precision with only 0.040mm error. This approach has the potential to substantially improve clinical workflows in periodontal disease management, offering a more precise, patient-friendly method for diagnosis and treatment decision-making.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 6","pages":"102186"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324517","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":"Disparities, trends, and projections of cancer mortality burden related to high body mass index in China from 2005 to 2030.","authors":"Yixin Tian, Xue Cao, Chenye Chang, Xin Wang, Congyi Zheng, Xuyan Pei, Xue Yu, Yujie Zhang, Nuerguli Tuerdi, Zhenping Zhao, Limin Wang, Peng Yin, Yuehui Fang, Mei Zhang, Yuna He, Maigeng Zhou, Zengwu Wang","doi":"10.1016/j.xcrm.2025.102137","DOIUrl":"10.1016/j.xcrm.2025.102137","url":null,"abstract":"<p><p>High body mass index (BMI), defined as a BMI greater than or equal to 20-25 kg/m<sup>2</sup>, is considered a rapid-increased risk factor for cancer. Based on comparative risk assessment framework, we elaborate the mortality burden of cancers attributable to high BMI in China. In 2018, we estimated that there were 85.19 thousand cancer-related deaths and 2,220.01 thousand cancer-related years of life lost (YLLs) attributable to high BMI in China. Of these, 62.14 thousand deaths and 1,698.81 thousand YLLs were from males. With higher socioeconomic levels, the burden generally increases initially and then decreases. By 2030, the projected age-standardized mortality rate attributable to high BMI in China will be 6.67 per 100,000 people, increased by 3.25% from that in 2005. In summary, the swift increase and substantial disparities in the cancer burden attributable to high BMI underscore the urgent need for evidence-based policies and interventions in China.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102137"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085960","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":"DDX5 super-enhancer promotes vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription.","authors":"Tian Xia, Haimeng Yin, Qingwen Zhu, Kaiwen Zhang, Haijing Xie, Ying Shan, Siyu Zhang, Rui Zhu, Keying Li, Mengyu Miao, Yingna Lu, Zhefang Wang, Jianmei Zhao, Yiwen You, Bo You","doi":"10.1016/j.xcrm.2025.102146","DOIUrl":"10.1016/j.xcrm.2025.102146","url":null,"abstract":"<p><p>Anti-angiogenic therapies (AATs) exhibit limited efficacy, as most patients with cancer inevitably develop resistance to them. In this study, data generated using a nasopharyngeal carcinoma orthotopic mouse model, combined with clinical data, reveal compensatory vasculogenic mimicry (VM) formation during AAT treatment and the association of VM with poor prognosis in nasopharyngeal carcinoma. Additionally, data-independent acquisition mass spectrometry-based proteomics shows that upregulation of a disintegrin And metalloprotease 10 (ADAM10) contributes to VM. Mechanistically, epigenetic and high-resolution chromatin interaction landscape analyses demonstrate that although ADAM10 does not interact with either the proximal or distal enhancers, DEAD-box helicase 5 (DDX5), a transcription factor of ADAM10, is regulated by long-range looping enhancer-promoter interactions. Further analyses identify transcription factors binding to critical constituents of the DDX5 super-enhancer. Ingenol mebutate, which docks excellently with DDX5, reverses ADAM10-mediated gene expression changes, thereby effectively suppressing compensatory VM formation and metastasis and improving prognosis. Collectively, these findings provide insights into the clinical application of AATs.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102146"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141488","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-06-02DOI: 10.1016/j.xcrm.2025.102159
Jack A Collora, Savannah F Steinhauser, Timothy C Davenport, Daniel C Lin, Amare Eshetu, Samana Zeidi, Rachel Kim, Cynthia Frank, Yuval Kluger, Sandra A Springer, Ya-Chi Ho
{"title":"Medications for opioid use disorder shape immune responses during chronic HIV infection.","authors":"Jack A Collora, Savannah F Steinhauser, Timothy C Davenport, Daniel C Lin, Amare Eshetu, Samana Zeidi, Rachel Kim, Cynthia Frank, Yuval Kluger, Sandra A Springer, Ya-Chi Ho","doi":"10.1016/j.xcrm.2025.102159","DOIUrl":"10.1016/j.xcrm.2025.102159","url":null,"abstract":"<p><p>People living with HIV (PLWHs) have higher risk of opioid use disorder (OUD). Whether medications for opioid use disorder (MOUDs) change immune responses in HIV infection is unknown. We examined the immune profiles in PLWHs before and 3 months after initiation of the μ opioid receptor agonist methadone, partial agonist buprenorphine, and antagonist naltrexone. Using single-cell DOGMA-seq, we profiled 29,462 peripheral blood immune cells in 12 PLWHs. We found that naltrexone treatment increased type I interferon (IFN) responses while buprenorphine increased tumor necrosis factor (TNF) responses in cytotoxic T cell population. We found that HIV+ cells in PLWHs with OUD upregulated PTPN13 and TAF5L, both of which are associated with HIV replication. We found trends suggesting increased HIV RNA expression after methadone and decreased HIV RNA expression after buprenorphine and naltrexone initiation. Overall, PLWHs treated with MOUD had improved immune responses and decreased HIV expression.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102159"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215049","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-06-06DOI: 10.1016/j.xcrm.2025.102163
Jeppe Kjærgaard, Cecilie B Lindqvist, Júlia Prats Quesada, Søren Jessen, Farina Schlabs, Amy M Ehrlich, Caio Y Yonamine, Mario García-Ureña, Johann H Schmalbruch, Lewin Small, Martin Thomassen, Anders Krogh Lemminger, Kasper Eibye, Alba Gonzalez-Franquesa, Jacob V Stidsen, Kurt Højlund, Juleen R Zierath, Tuomas O Kilpeläinen, Jens Bangsbo, Jonas T Treebak, Morten Hostrup, Atul S Deshmukh
{"title":"Insulin- and exercise-induced phosphoproteomics of human skeletal muscle identify REPS1 as a regulator of muscle glucose uptake.","authors":"Jeppe Kjærgaard, Cecilie B Lindqvist, Júlia Prats Quesada, Søren Jessen, Farina Schlabs, Amy M Ehrlich, Caio Y Yonamine, Mario García-Ureña, Johann H Schmalbruch, Lewin Small, Martin Thomassen, Anders Krogh Lemminger, Kasper Eibye, Alba Gonzalez-Franquesa, Jacob V Stidsen, Kurt Højlund, Juleen R Zierath, Tuomas O Kilpeläinen, Jens Bangsbo, Jonas T Treebak, Morten Hostrup, Atul S Deshmukh","doi":"10.1016/j.xcrm.2025.102163","DOIUrl":"10.1016/j.xcrm.2025.102163","url":null,"abstract":"<p><p>Skeletal muscle glucose uptake, essential for metabolic health, is regulated by both insulin and exercise. Using phosphoproteomics, we analyze skeletal muscle from healthy individuals following acute exercise or insulin stimulation, generating a valuable dataset. We identify 71 phosphosites on 55 proteins regulated by both stimuli in the same direction, suggesting a convergence of exercise and insulin signaling pathways. Among these, the vesicle-associated protein, REPS1, is highly phosphorylated at Ser709 in response to both stimuli. We identify p90 ribosomal S6 kinase (RSK) to be a key upstream kinase of REPS1 S709 phosphorylation and that the RSK-REPS1 signaling axis is involved in insulin-stimulated glucose uptake. Insulin-induced REPS1 Ser709 phosphorylation is closely linked to muscle and whole-body insulin sensitivity and is impaired in insulin-resistant mice and humans. These findings highlight REPS1 as a convergence point for insulin and exercise signaling, presenting a potential therapeutic target for treating individuals with insulin resistance.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102163"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246605","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":"Ultra-wide-field fundus photography and AI-based screening and referral for multiple ocular fundus diseases.","authors":"Xinyu Zhao, Xingwang Gu, Da Teng, Xiaolei Sun, Qijie Wei, Bo Wang, Jinrui Wang, Jianchun Zhao, Dayong Ding, Bilei Zhang, Yuelin Wang, Wenfei Zhang, Shiyu Cheng, Xinyu Liu, Lihui Meng, Bing Li, Xiao Zhang, Zhengming Shi, Anyi Liang, Guofang Jiao, Huiqin Lu, Changzheng Chen, Rishet Ahmat, Hao Zhang, Yakun Li, Dan Zhu, Han Zhang, Hongbin Lv, Donglei Zhang, Mengda Li, Ziwu Zhang, Ling Yuan, Chang Su, Dawei Sun, Qiuming Li, Dawa Xiao, Youxin Chen","doi":"10.1016/j.xcrm.2025.102187","DOIUrl":"10.1016/j.xcrm.2025.102187","url":null,"abstract":"<p><p>To address the difficulty in comprehensive screening of fundus diseases, we develop three deep learning algorithms (DLAs) based on different algorithms (Swin Transformer and cross-domain collaborative learning [CdCL]) and imaging modalities (ultra-wide-field [UWF] images and the cropped posterior-pole-region [PPR] images) to identify 25 fundus conditions and provide referral suggestions: WARM (CdCL + UWF images), BASE (Swin Transformer + UWF images), and WARM-PPR (CdCL + PPR images). 59,475 UWF images are included to establish internal and external datasets. WARM shows the best performance on the internal test (area under the receiver operating characteristic curve [AUC] for screening = 0.915; AUC for referral = 0.911) and the external multi-center test (AUC for screening = 0.912; AUC for referral = 0.902). UWF images and the CdCL approach significantly enhance the DLA's ability to detect abnormalities in the peripheral retina. The WARM model shows promise as a reliable and accurate tool for comprehensive fundus screening on a large scale.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102187"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274285","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}
Caroline Laheurte, Laura Boullerot, Babacar Ndao, Marine Malfroy, Lise Queiroz, Phillippe Guillaume, Romain Loyon, Evan Seffar, Eleonore Gravelin, Adeline Renaudin, Marion Jacquin, Aurélia Meurisse, Dewi Vernerey, François Ghiringhelli, Yann Godet, Raphael Genoley, Camilla Jandus, Christophe Borg, Olivier Adotévi
{"title":"UCPVax, a CD4 helper peptide vaccine, induces polyfunctional Th1 cells, antibody response, and epitope spreading to improve antitumor immunity.","authors":"Caroline Laheurte, Laura Boullerot, Babacar Ndao, Marine Malfroy, Lise Queiroz, Phillippe Guillaume, Romain Loyon, Evan Seffar, Eleonore Gravelin, Adeline Renaudin, Marion Jacquin, Aurélia Meurisse, Dewi Vernerey, François Ghiringhelli, Yann Godet, Raphael Genoley, Camilla Jandus, Christophe Borg, Olivier Adotévi","doi":"10.1016/j.xcrm.2025.102196","DOIUrl":"10.1016/j.xcrm.2025.102196","url":null,"abstract":"<p><p>The induction of an antitumor CD4<sup>+</sup> T helper response is essential for the efficacy of therapeutic cancer vaccines. However, few vaccines are specifically designed to target CD4<sup>+</sup> T cells in human cancers. Here, we characterize the immune mechanisms of UCPVax, a helper peptide vaccine derived from telomerase. Ex vivo immune profiling of peripheral blood from 60 patients with advanced lung cancer reveals that UCPVax selectively activates CD4<sup>+</sup> T cells in vivo across a broad HLA-DR restriction. The vaccine elicits a synergistic immune triad, including cytokine polyfunctional CD4<sup>+</sup> Th1 cells, epitope spreading, and antibody response, contributing to effective tumor control. Single-cell analysis further demonstrates that UCPVax drives CD4<sup>+</sup> T cells toward effector memory and cytolytic differentiation. Thus, vaccine-induced CD4<sup>+</sup> T cells trigger broad and durable antitumor immunity. These findings highlight UCPVax as an off-the-shelf helper platform to enhance therapeutic cancer vaccine efficacy. This study was registered at ClinicalTrials.gov: NCT02818426.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102196"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339958","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-05-22DOI: 10.1016/j.xcrm.2025.102144
Zhi Yang, Yizheng Yao, Xi Chen, Victoria Madigan, Shanrui Pu, Xianqun Fan, Jun Pu, Fengfeng Bei
{"title":"Cross-species tropism of AAV.CPP.16 in the respiratory tract and its gene therapies against pulmonary fibrosis and viral infection.","authors":"Zhi Yang, Yizheng Yao, Xi Chen, Victoria Madigan, Shanrui Pu, Xianqun Fan, Jun Pu, Fengfeng Bei","doi":"10.1016/j.xcrm.2025.102144","DOIUrl":"10.1016/j.xcrm.2025.102144","url":null,"abstract":"<p><p>Efficient gene delivery vectors are crucial for respiratory and lung disease therapies. We report that AAV.CPP.16, an engineered adeno-associated virus (AAV) variant derived from AAV9, efficiently transduces airway and lung cells in mice and non-human primates via intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism for respiratory tissues, and efficiently targets key respiratory cell types. It supports gene supplementation and editing therapies in two clinically relevant mouse models of respiratory and lung diseases. A single intranasal dose of AAV.CPP.16 expressing a dual-target, vascular endothelial growth factor (VEGF)/transforming growth factor (TGF)-β1-neutralizing protein protected lungs from idiopathic pulmonary fibrosis, while a similar application of AAV.CPP.16 carrying an \"all-in-one\" CRISPR-Cas13d system inhibited transcription of the SARS-CoV-2-derived RNA-dependent RNA polymerase (Rdrp) gene. Our findings highlight AAV.CPP.16 as a promising vector for respiratory and lung gene therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102144"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131841","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-06-03DOI: 10.1016/j.xcrm.2025.102157
Anastasia Conti, Kety Giannetti, Federico Midena, Stefano Beretta, Nicolò Gualandi, Rosaria De Marco, Edoardo Carsana, Angelica Varesi, Teresa Tavella, Laura Alessandrini, Parinaz Zarghamian, Alessandra Weber, Samuele Ferrari, Chiara Brombin, Diego Gilioli, Lucrezia Della Volpe, Stephanie Z Xie, Ivan Merelli, Toni Cathomen, Luigi Naldini, Raffaella Di Micco
{"title":"Senescence and inflammation are unintended adverse consequences of CRISPR-Cas9/AAV6-mediated gene editing in hematopoietic stem cells.","authors":"Anastasia Conti, Kety Giannetti, Federico Midena, Stefano Beretta, Nicolò Gualandi, Rosaria De Marco, Edoardo Carsana, Angelica Varesi, Teresa Tavella, Laura Alessandrini, Parinaz Zarghamian, Alessandra Weber, Samuele Ferrari, Chiara Brombin, Diego Gilioli, Lucrezia Della Volpe, Stephanie Z Xie, Ivan Merelli, Toni Cathomen, Luigi Naldini, Raffaella Di Micco","doi":"10.1016/j.xcrm.2025.102157","DOIUrl":"10.1016/j.xcrm.2025.102157","url":null,"abstract":"<p><p>Gene editing (GE) using homology-directed repair (HDR) in hematopoietic stem and progenitor cells (HSPCs) offers promise for long-range gene correction of inherited genetic disorders. However, cellular responses induced by CRISPR-Cas9/AAV6 engineering impair the long-term repopulating potential of HDR-edited HSPCs, adversely impacting the safety and efficacy of clinical translation. Our study uncovers a durable senescence-like response in genetically engineered HSPCs triggered by p53 and interleukin (IL)-1/nuclear factor κB (NF-κB) activation, which restricts graft size and clonal diversity in long-term transplantation assays. We show that transient p53 inhibition or blocking inflammatory pathways mitigates senescence-associated responses, improving the repopulating capacity of edited HSPCs. Importantly, we identify treatment with Anakinra, an IL-1 signaling antagonist, as a promising strategy to enhance polyclonal output in HDR-edited cells while minimizing genotoxicity risks associated with the editing procedure. Overall, our findings present strategies to overcome key hurdles in HDR-based HSPC gene therapies, providing a framework for enhancing their efficacy and safety in clinical applications.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102157"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224434","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-05-29DOI: 10.1016/j.xcrm.2025.102150
Benjamin Bone, Nicola Cotugno, Chiara Pighi, Arianna Rotili, Seohyun Hong, Leah Carrere, Elena Morrocchi, Giuseppe Rubens Pascucci, Ce Gao, Nicole Colantoni, Weiwei Sun, Giovanna Leone, David R Collins, Mpho J Olatotse, Giovanna Del Principe, Toong Seng Tan, Melanie Lancien, Alessia Neri, Libera Sessa, Giulio Olivieri, Kailey Shapiro, Isabelle Roseto, Catherine Koofhethile, Elena Emili, Stefania Bernardi, Ann Chahroudi, Paolo Rossi, Bruce D Walker, Xu G Yu, Mathias Lichterfeld, Paolo Palma
{"title":"Distinct viral reservoirs and immune signatures in individuals on long-term antiretroviral therapy with perinatally acquired HIV-1.","authors":"Benjamin Bone, Nicola Cotugno, Chiara Pighi, Arianna Rotili, Seohyun Hong, Leah Carrere, Elena Morrocchi, Giuseppe Rubens Pascucci, Ce Gao, Nicole Colantoni, Weiwei Sun, Giovanna Leone, David R Collins, Mpho J Olatotse, Giovanna Del Principe, Toong Seng Tan, Melanie Lancien, Alessia Neri, Libera Sessa, Giulio Olivieri, Kailey Shapiro, Isabelle Roseto, Catherine Koofhethile, Elena Emili, Stefania Bernardi, Ann Chahroudi, Paolo Rossi, Bruce D Walker, Xu G Yu, Mathias Lichterfeld, Paolo Palma","doi":"10.1016/j.xcrm.2025.102150","DOIUrl":"10.1016/j.xcrm.2025.102150","url":null,"abstract":"<p><p>Early initiation of antiretroviral therapy (ART) following HIV-1 infection restricts the size of the latent reservoir, following both horizontal and vertical infections. Here, we comprehensively profile the reservoirs and immunological milieus of nine young adults who acquired HIV-1 perinatally and remained on suppressive long-term ART (median: 20 years) since infancy (LeukoHIV cohort). Genome-intact reservoirs are markedly smaller compared to a cohort of adults on suppressive ART started in adulthood, with some LeukoHIV individuals characterized by an absence or near absence of intact proviruses in up to a billion peripheral blood mononuclear cells (PBMCs). Higher frequencies of functional CD56<sup>bright</sup> natural killer (NK) cells with increased cytotoxic activity are detectable in the LeukoHIV cohort compared to an adult reference cohort, while one LeukoHIV participant displayed a potent HIV-1-specific CD8<sup>+</sup> T cell response. Collectively, our data suggest that long-term ART initiated in early life following perinatal transmission may facilitate an immune environment better equipped to restrict the HIV-1 reservoir.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102150"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186613","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}
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