{"title":"CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors.","authors":"Bihui Cao, Manting Liu, Zecong Xiao, Dongliang Leng, Yubo Zhou, Zhenfeng Zhang, Lu Wang, Xinkun Huang, Qianqian Ni, Wei Cheng, Yehuda G Assaraf, Qi Zhao, Jia Shen, Kangshun Zhu","doi":"10.1016/j.xcrm.2025.101965","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.101965","url":null,"abstract":"<p><p>Microwave ablation (MWA) triggers a weak systemic immune response that leads to the abscopal regression of distant metastases while killing local tumors, known as the abscopal effect. Combining MWA with chimeric antigen receptor (CAR)-T cells demonstrates promise in enhancing the abscopal effect in antigen-homogeneous tumors. However, the loss of the antigen recognized by CAR or intrinsic antigenic heterogeneity in solid tumors poses a major obstacle. SIRPα variant (CV1)-secreting CAR-T (sCAR-T) cells elicit an abscopal effect on distant tumors with antigen heterogeneity in mice receiving local MWA. Mechanistically, sCAR-T cells can locally eliminate antigen-positive tumors and secrete CV1, whereas the secreted CV1 can activate macrophages that migrate to non-ablated tumor sites in response to post-MWA chemokines, eliciting a macrophage-dependent abscopal effect that enables phagocytosis of antigen-heterogeneous cancer cells. This macrophage-dependent abscopal effect instigated by MWA and sCAR-T cells offers a clinically translatable strategy in metastatic solid tumors with antigen heterogeneity.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 2","pages":"101965"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457055","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 : 2025-02-18Epub Date: 2025-01-30DOI: 10.1016/j.xcrm.2025.101931
Thomas Look, Roman Sankowski, Manon Bouzereau, Serena Fazio, Miaomiao Sun, Alicia Buck, Niklas Binder, Maximilian Mastall, Francesco Prisco, Frauke Seehusen, Julia Frei, Conrad Wyss, Berend Snijder, Cesar Nombela Arrieta, Michael Weller, Steve Pascolo, Tobias Weiss
{"title":"CAR T cells, CAR NK cells, and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines.","authors":"Thomas Look, Roman Sankowski, Manon Bouzereau, Serena Fazio, Miaomiao Sun, Alicia Buck, Niklas Binder, Maximilian Mastall, Francesco Prisco, Frauke Seehusen, Julia Frei, Conrad Wyss, Berend Snijder, Cesar Nombela Arrieta, Michael Weller, Steve Pascolo, Tobias Weiss","doi":"10.1016/j.xcrm.2025.101931","DOIUrl":"10.1016/j.xcrm.2025.101931","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. In vitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101931"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073937","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 : 2025-02-18Epub Date: 2025-02-04DOI: 10.1016/j.xcrm.2025.101934
Florent Peyraud, Jean-Philippe Guégan, Christophe Rey, Oren Lara, Ophélie Odin, Marie Del Castillo, Lucile Vanhersecke, Jean-Michel Coindre, Emma Clot, Maxime Brunet, Thomas Grellety, Angélique Tasseel, Sylvestre Le Moulec, Robert J Johnston, Alban Bessede, Antoine Italiano
{"title":"Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures.","authors":"Florent Peyraud, Jean-Philippe Guégan, Christophe Rey, Oren Lara, Ophélie Odin, Marie Del Castillo, Lucile Vanhersecke, Jean-Michel Coindre, Emma Clot, Maxime Brunet, Thomas Grellety, Angélique Tasseel, Sylvestre Le Moulec, Robert J Johnston, Alban Bessede, Antoine Italiano","doi":"10.1016/j.xcrm.2025.101934","DOIUrl":"10.1016/j.xcrm.2025.101934","url":null,"abstract":"<p><p>Effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) has been linked to the presence of mature tertiary lymphoid structures (mTLSs) within the tumor microenvironment (TME). However, only a subset of mTLS-positive NSCLC derives benefit, thus highlighting the need to unravel ICI response determinants. The comprehensive analysis of ICI-treated patients with NSCLC (n = 509) from the Bergonié Institute Profiling (BIP) study (NCT02534649) reveals that the presence of mTLSs correlates with improved clinical outcomes, independently of programmed death ligand 1 (PD-L1) expression and genomic features. Employing spatial transcriptomics alongside multiplex immunofluorescence (mIF), we show that two distinct subsets of cancer-associated fibroblasts (CAFs) are essential factors in mediating primary resistance to ICIs in mTLS-positive NSCLC. These CAFs are associated with immune exclusion, CD8<sup>+</sup> T cell exhaustion, and increased regulatory CD4<sup>+</sup> T cell infiltration, underscoring an immunosuppressive TME. Our study highlights the pivotal role of specific CAF subsets in thwarting ICIs, proposing new therapeutic targets to enhance immunotherapy efficacy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101934"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254784","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 : 2025-02-18Epub Date: 2025-02-10DOI: 10.1016/j.xcrm.2025.101964
Sarah-Eve Lemay, Manon Mougin, Mélanie Sauvaget, Reem El Kabbout, Chanil Valasarajan, Keiko Yamamoto, Sandra Martineau, Andréanne Pelletier, Coralie Bilodeau, Yann Grobs, Alice Bourgeois, Charlotte Romanet, Sandra Breuils-Bonnet, Monica S Montesinos, Min Lu, Huidong Chen, Mégan Gilbert, Charlie Théberge, François Potus, Soni Pullamsetti, Steeve Provencher, Sébastien Bonnet, Olivier Boucherat
{"title":"Unraveling AURKB as a potential therapeutic target in pulmonary hypertension using integrated transcriptomic analysis and pre-clinical studies.","authors":"Sarah-Eve Lemay, Manon Mougin, Mélanie Sauvaget, Reem El Kabbout, Chanil Valasarajan, Keiko Yamamoto, Sandra Martineau, Andréanne Pelletier, Coralie Bilodeau, Yann Grobs, Alice Bourgeois, Charlotte Romanet, Sandra Breuils-Bonnet, Monica S Montesinos, Min Lu, Huidong Chen, Mégan Gilbert, Charlie Théberge, François Potus, Soni Pullamsetti, Steeve Provencher, Sébastien Bonnet, Olivier Boucherat","doi":"10.1016/j.xcrm.2025.101964","DOIUrl":"10.1016/j.xcrm.2025.101964","url":null,"abstract":"<p><p>Despite advances in treatment, the prognosis for patients with pulmonary arterial hypertension (PAH) remains dismal, highlighting the need for further therapeutic advances. By using RNA sequencing on pulmonary artery smooth muscle cells (PASMCs), functional enrichment, and connectivity map analyses, we identify Aurora kinase B (AURKB) as a candidate therapeutic target. We show that AURKB inhibition blocks cell cycle progression and reverses the gene signature of PAH-PASMCs. We also report that PAH-PASMCs that escape apoptosis acquire a senescence-associated secretory phenotype. In vivo, AURKB inhibition using barasertib improves hemodynamics in two preclinical models of established PAH by attenuating pulmonary vascular remodeling. A therapeutic effect is also observed in human precision-cut lung slices. Finally, we demonstrate that the combination of barasertib with a p21 attenuator is more effective in reducing vascular remodeling than either drug alone. These findings provide insight into strategies for therapeutic manipulation.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101964"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398481","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":"Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.","authors":"Xie Song, Zijie Xia, Dayne Martinez, Bing Xu, Zachary Spritzer, Yanjie Zhang, Erin Nugent, Yugong Ho, Barbara Terzic, Zhaolan Zhou","doi":"10.1016/j.xcrm.2024.101926","DOIUrl":"10.1016/j.xcrm.2024.101926","url":null,"abstract":"<p><p>Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental syndrome caused by mutations in the X-linked CDKL5 gene. The early onset of CDD suggests that CDKL5 is essential during development, but post-developmental re-expression rescues multiple CDD-related phenotypes in hemizygous male mice. Since most patients are heterozygous females, studies in clinically relevant female models are essential. Here, we systematically compare phenotype reversal across age and sex using two independent mouse models of CDD. We find that early re-activation of endogenous Cdkl5 in heterozygous females reverses most phenotypes, except working memory. Later re-expression improves several traits but has limited effects on cognitive function. Seizure prevention is more effective with early intervention in heterozygous females but becomes limited after seizure onset. These findings demonstrate the robust potential of CDKL5 re-expression to reverse CDD-related phenotypes in both sexes while underscoring the critical impact of age and disease stage in designing clinical trials.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101926"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037334","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 : 2025-02-18Epub Date: 2025-01-28DOI: 10.1016/j.xcrm.2024.101916
Samuele Cortese, Alessio Bellato, Alessandra Gabellone, Lucia Marzulli, Emilia Matera, Valeria Parlatini, Maria Giuseppina Petruzzelli, Antonio M Persico, Richard Delorme, Paolo Fusar-Poli, Corentin J Gosling, Marco Solmi, Lucia Margari
{"title":"Latest clinical frontiers related to autism diagnostic strategies.","authors":"Samuele Cortese, Alessio Bellato, Alessandra Gabellone, Lucia Marzulli, Emilia Matera, Valeria Parlatini, Maria Giuseppina Petruzzelli, Antonio M Persico, Richard Delorme, Paolo Fusar-Poli, Corentin J Gosling, Marco Solmi, Lucia Margari","doi":"10.1016/j.xcrm.2024.101916","DOIUrl":"10.1016/j.xcrm.2024.101916","url":null,"abstract":"<p><p>The diagnosis of autism is currently based on the developmental history, direct observation of behavior, and reported symptoms, supplemented by rating scales/interviews/structured observational evaluations-which is influenced by the clinician's knowledge and experience-with no established diagnostic biomarkers. A growing body of research has been conducted over the past decades to improve diagnostic accuracy. Here, we provide an overview of the current diagnostic assessment process as well as of recent and ongoing developments to support diagnosis in terms of genetic evaluation, telemedicine, digital technologies, use of machine learning/artificial intelligence, and research on candidate diagnostic biomarkers. Genetic testing can meaningfully contribute to the assessment process, but caution is required when interpreting negative results, and more work is needed to strengthen the transferability of genetic information into clinical practice. Digital diagnostic and machine-learning-based analyses are emerging as promising approaches, but larger and more robust studies are needed. To date, there are no available diagnostic biomarkers. Moving forward, international collaborations may help develop multimodal datasets to identify biomarkers, ensure reproducibility, and support clinical translation.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101916"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064204","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 : 2025-02-18Epub Date: 2025-01-18DOI: 10.1016/j.xcrm.2025.101944
Subhamoy Chakraborty, Utsav Sen, Kedwin Ventura, Vrinda Jethalia, Charles Coleman, Subhasree Sridhar, Avisek Banerjee, Hilal Ozakinci, Yazhini Mahendravarman, Konrad Snioch, Elisa de Stanchina, Misty D Shields, Lewis E Tomalin, Deniz Demircioglu, Theresa A Boyle, Anna Tocheva, Dan Hasson, Triparna Sen
{"title":"Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer.","authors":"Subhamoy Chakraborty, Utsav Sen, Kedwin Ventura, Vrinda Jethalia, Charles Coleman, Subhasree Sridhar, Avisek Banerjee, Hilal Ozakinci, Yazhini Mahendravarman, Konrad Snioch, Elisa de Stanchina, Misty D Shields, Lewis E Tomalin, Deniz Demircioglu, Theresa A Boyle, Anna Tocheva, Dan Hasson, Triparna Sen","doi":"10.1016/j.xcrm.2025.101944","DOIUrl":"10.1016/j.xcrm.2025.101944","url":null,"abstract":"","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101944"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000989","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":"Advanced image-identified extranodal extension of retropharyngeal lymph nodes in the refinement of N classification for nasopharyngeal carcinoma.","authors":"Wei Jiang, Gao-Yuan Wang, Guan-Jie Qin, Wu-Qi Zhang, Xiao-Dong Zhu, Ya-Qian Han, Feng Lei, Liang-Fang Shen, Kun-Yu Yang, Chun-Yan Cui, Ling-Long Tang, Yan-Ping Mao, Lei Chen, Rui Guo, Ling Li, Zheng Wu, Gui-Qiong Xu, Qin Zhou, Jing Huang, Shao-Hui Huang, Ji-Bin Li, Li-Zhi Liu, Jun Ma, Xiao-Jing Du","doi":"10.1016/j.xcrm.2025.101942","DOIUrl":"10.1016/j.xcrm.2025.101942","url":null,"abstract":"<p><p>Advanced extranodal extension (ENE) in cervical lymph nodes (CLNs) increases the risk of distant metastasis in nasopharyngeal carcinoma (NPC). The 9th NPC staging system classifies N1/N2 patients with advanced CLN ENE as N3 due to similar outcomes. However, the prognostic impact of advanced ENE in retropharyngeal lymph nodes (RLNs) remains unclear. In this study of 4,485 patients with non-metastatic NPC, N1/N2 patients with advanced RLN ENE demonstrate better 5-year overall survival (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.38-0.93; HR: 0.57, 95% CI: 0.32-1.00) and failure-free survival (HR: 0.63, 95% CI: 0.44-0.92; HR: 0.52, 95% CI: 0.31-0.86) than N3 patients. Advanced RLN ENE shows a positive correlation with other RLN-related anatomical factors and is not identified as an independent prognostic factor. External validation in 3,849 patients from five centers supports these findings. Based on this evidence, upgrading advanced RLN ENE to N3 is not advised.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101942"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406010","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":"Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis.","authors":"Xuqing Shen, Yueyue Chen, Yingying Tang, Ping Lu, Mingzhu Liu, Tiebo Mao, Yawen Weng, Feier Yu, Yimei Liu, Yujie Tang, Liwei Wang, Ningning Niu, Jing Xue","doi":"10.1016/j.xcrm.2025.101928","DOIUrl":"10.1016/j.xcrm.2025.101928","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute to the metabolic flexibility and PDAC's response and adaptation to Gln scarcity in the tumor milieu remains largely unknown. Here, we elucidate that prolonged Gln restriction or treatment with the Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads to growth inhibition and ferroptosis program activation in PDAC. A CRISPR-Cas9 screen identifies an epigenetic regulator, Paxip1, which promotes H3K4me3 upregulation and Hmox1 transcription upon DON treatment. Additionally, ferroptosis-related repressors (e.g., Slc7a11 and Gpx4) are increased as an adaptive response, thereby predisposing PDAC cells to ferroptosis upon Gln deprivation. Moreover, DON sensitizes PDAC cells to GPX4 inhibitor-induced ferroptosis, both in vitro and in patient-derived xenografts (PDXs). Taken together, our findings reveal that targeting Gln dependency confers susceptibility to GPX4-dependent ferroptosis via epigenetic remodeling and provides a combination strategy for PDAC therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101928"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064208","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 : 2025-02-18Epub Date: 2025-02-11DOI: 10.1016/j.xcrm.2025.101946
Antonio Santos-Peral, Magdalena Zaucha, Elena Nikolova, Ekin Yaman, Barbara Puzek, Elena Winheim, Sebastian Goresch, Magdalena K Scheck, Lisa Lehmann, Frank Dahlstroem, Hadi Karimzadeh, Julia Thorn-Seshold, Shenzhi Jia, Fabian Luppa, Michael Pritsch, Julia Butt, Camila Metz-Zumaran, Giovanna Barba-Spaeth, Stefan Endres, Sarah Kim-Hellmuth, Tim Waterboer, Anne B Krug, Simon Rothenfusser
{"title":"Basal T cell activation predicts yellow fever vaccine response independently of cytomegalovirus infection and sex-related immune variations.","authors":"Antonio Santos-Peral, Magdalena Zaucha, Elena Nikolova, Ekin Yaman, Barbara Puzek, Elena Winheim, Sebastian Goresch, Magdalena K Scheck, Lisa Lehmann, Frank Dahlstroem, Hadi Karimzadeh, Julia Thorn-Seshold, Shenzhi Jia, Fabian Luppa, Michael Pritsch, Julia Butt, Camila Metz-Zumaran, Giovanna Barba-Spaeth, Stefan Endres, Sarah Kim-Hellmuth, Tim Waterboer, Anne B Krug, Simon Rothenfusser","doi":"10.1016/j.xcrm.2025.101946","DOIUrl":"10.1016/j.xcrm.2025.101946","url":null,"abstract":"<p><p>The live-attenuated yellow fever 17D (YF17D) vaccine is a model of acute viral infection that induces long-lasting protective immunity. Among immunocompetent adults, responses to YF17D vary significantly. To understand the sources of this variability, we investigate the influence of sex, age, human leukocyte antigen (HLA) type, and 20 prior infections on basal immune parameters and the cellular and antibody response to YF17D in 250 healthy young individuals. Multivariate regression found that sex and cytomegalovirus (CMV) infection significantly contribute to baseline immune variation but do not affect vaccine responses except for reduced YF17D-specific CD8<sup>+</sup> frequencies in CMV-infected males. However, the abundance at baseline of non-specific cytokine-expressing T helper cells in circulation is associated with stronger vaccine responses, a state that smoking favors. Additionally, an elevated baseline level of interferon-stimulated CXCL10 is linked to poorer vaccination outcomes. Altogether, YF17D reactivity is conditioned by the baseline immune status independent of sex and CMV-related variations.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101946"},"PeriodicalIF":11.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406011","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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