Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-31DOI: 10.1016/j.xcrm.2025.102245
Umair Khan, Tomiko T Oskotsky, Bahar D Yilmaz, Jacquelyn Roger, Ketrin Gjoni, Juan C Irwin, Jessica Opoku-Anane, Noémie Elhadad, Linda C Giudice, Marina Sirota
{"title":"Comorbidity analysis and clustering of endometriosis patients using electronic health records.","authors":"Umair Khan, Tomiko T Oskotsky, Bahar D Yilmaz, Jacquelyn Roger, Ketrin Gjoni, Juan C Irwin, Jessica Opoku-Anane, Noémie Elhadad, Linda C Giudice, Marina Sirota","doi":"10.1016/j.xcrm.2025.102245","DOIUrl":"10.1016/j.xcrm.2025.102245","url":null,"abstract":"<p><p>Endometriosis is a prevalent, complex, inflammatory condition associated with a diverse range of symptoms and comorbidities. Despite its substantial burden on patients, population-level studies that explore its comorbid patterns and heterogeneity are limited. In this retrospective case-control study, we analyze comorbidities from over forty thousand endometriosis patients across six University of California medical centers using de-identified electronic health record (EHR) data. We find hundreds of conditions significantly associated with endometriosis, including genitourinary disorders, neoplasms, and autoimmune diseases, with strong replication across datasets. Clustering analyses identify patient subpopulations with distinct comorbidity patterns, including psychiatric and autoimmune conditions. This study provides a comprehensive analysis of endometriosis comorbidities and highlights the heterogeneity within the patient population. Our findings demonstrate the utility of EHR data in uncovering clinically meaningful patterns and suggest pathways for personalized disease management and future research on biological mechanisms underlying endometriosis.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102245"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764633","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-08-05DOI: 10.1016/j.xcrm.2025.102276
Fangyoumin Feng, Tian He, Ping Lin, Jinwu Hu, Bihan Shen, Zhixuan Tang, Jian Zhou, Jia Fan, Bo Hu, Hong Li
{"title":"Computational framework for prioritizing candidate compounds overcoming the resistance of pancancer immunotherapy.","authors":"Fangyoumin Feng, Tian He, Ping Lin, Jinwu Hu, Bihan Shen, Zhixuan Tang, Jian Zhou, Jia Fan, Bo Hu, Hong Li","doi":"10.1016/j.xcrm.2025.102276","DOIUrl":"10.1016/j.xcrm.2025.102276","url":null,"abstract":"<p><p>Combination therapy has emerged as an effective approach to overcome resistance to immunotherapy. However, only a small number of drugs have been identified with synergistic effects with immunotherapy. Here, we develop a computational framework (IGeS-BS) to recommend compounds that potentially overcome resistance to immunotherapy. A meta-analysis of approximately 1,000 transcriptomes from immunotherapy patients revealed 33 tumor microenvironment (TME) signatures that can robustly and accurately estimate immunotherapy responses. An immuno-boosting landscape for more than 10,000 compounds and 13 cancer types was subsequently generated on The Cancer Genome Atlas (TCGA) and The Library of Integrated Network-Based Cellular Signatures (LINCS) datasets. Furthermore, the immuno-boosting effects of several high-scoring compounds were evaluated by in vitro and in vivo experiments in hepatocellular carcinoma and other cancer types. The results showed that the two best compounds (SB-366791 and CGP-60474) significantly alleviate the resistance of hepatocellular carcinoma to anti-PD1 therapy by activating immune cells. Collectively, our research provides an efficient framework for discovering compounds that enhance immunotherapy responses.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102276"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793572","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}
Lev Petrov, Sophia Brumhard, Sebastian Wisniewski, Philipp Georg, David Hillus, Anna Hiller, Rosario Astaburuaga-García, Nils Blüthgen, Emanuel Wyler, Katrin Vogt, Hannah-Philine Dey, Saskia von Stillfried, Christina Iwert, Roman D Bülow, Bruno Märkl, Lukas Maas, Christine Langner, Tim Meyer, Jennifer Loske, Roland Eils, Irina Lehmann, Benjamin Ondruschka, Markus Ralser, Jakob Trimpert, Peter Boor, Sammy Bedoui, Christian Meisel, Marcus A Mall, Victor M Corman, Leif Erik Sander, Jobst Röhmel, Birgit Sawitzki
{"title":"Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.","authors":"Lev Petrov, Sophia Brumhard, Sebastian Wisniewski, Philipp Georg, David Hillus, Anna Hiller, Rosario Astaburuaga-García, Nils Blüthgen, Emanuel Wyler, Katrin Vogt, Hannah-Philine Dey, Saskia von Stillfried, Christina Iwert, Roman D Bülow, Bruno Märkl, Lukas Maas, Christine Langner, Tim Meyer, Jennifer Loske, Roland Eils, Irina Lehmann, Benjamin Ondruschka, Markus Ralser, Jakob Trimpert, Peter Boor, Sammy Bedoui, Christian Meisel, Marcus A Mall, Victor M Corman, Leif Erik Sander, Jobst Röhmel, Birgit Sawitzki","doi":"10.1016/j.xcrm.2025.102285","DOIUrl":"10.1016/j.xcrm.2025.102285","url":null,"abstract":"<p><p>Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of 164 samples from SARS-CoV-2-infected persons aged 1 to 84 years reveals a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4<sup>+</sup> T cells, and B cells with increasing age. Diversion of IFN signaling is associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4<sup>+</sup> T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69<sup>high</sup> GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 8","pages":"102285"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944880","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":"BRD9 inhibition overcomes oncolytic virus therapy resistance in glioblastoma.","authors":"Chen Guo, Zhilin Long, Peng Lin, Yinan Shen, Yiye Zhong, Jingjing Qian, Jichuan Yu, Weixi Zhao, Fuyi Liu, Yiling Ma, Jian Zheng, Jiayao Yang, Shuai Zhao, Xiaojuan Ran, Zhen Xia, Congying Wu, Yujia Cai, Chen Wang, Qi Xie","doi":"10.1016/j.xcrm.2025.102258","DOIUrl":"10.1016/j.xcrm.2025.102258","url":null,"abstract":"<p><p>Long-term survival of glioblastoma multiforme (GBM) remains challenging, spurring the development of novel therapies such as oncolytic virus therapy. While oncolytic virus shows promise in clinical trials, many patients do not respond to this therapy. Here, we perform a CRISPR screening and identify the non-canonical BRG1/BRM-associated factor (ncBAF) complex as a pivotal tumor-intrinsic factor for oncolytic virotherapy resistance. Knocking out the ncBAF-specific subunit bromodomain-containing protein 9 (BRD9) markedly augments the oncolytic efficacy of oncolytic herpes simplex virus type 1 (oHSV1) and enhances antitumor immunity. Mechanistically, BRD9 binds to RELA and potentiates the expression of downstream antiviral genes. Notably, the application of BRD9 inhibitor (IBRD9) significantly enhances the oncolytic activity of oHSV1 in various GBM models. Moreover, reduced BRD9 levels strongly correlate with improved outcomes in clinical trials of oHSV1. These findings suggest that BRD9 is an attractive target for overcoming the resistance to oHSV1 in glioblastoma treatment.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102258"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759280","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":"A CD147-targeted small-molecule inhibitor potentiates gemcitabine efficacy by triggering ferroptosis in pancreatic ductal adenocarcinoma.","authors":"Jiaqi Li, Chaozhe Ma, Pei Cao, Weihua Guo, Pengyu Wang, Yang Yang, Bowen Ding, Fengyi Yin, Zhe Li, Yifei Wang, Shouyi Li, Chongbiao Huang, Xiuchao Wang, Tianxing Zhou, Antao Chang, Liang Zhao, Song Gao, Tiansuo Zhao, Hongwei Wang, Jun Yu, Jingyuan Xu, Yukuan Feng, Jihui Hao","doi":"10.1016/j.xcrm.2025.102292","DOIUrl":"10.1016/j.xcrm.2025.102292","url":null,"abstract":"<p><p>CD147 has emerged as a promising tumor-specific therapeutic target. Identifying small-molecule inhibitors that promote its proteolysis represents a critical step toward advancing clinical translation, while elucidating its mechanisms of action could further accelerate this process. In this study, we identify dracorhodin perchlorate (DP) as a potent CD147 inhibitor that induces autophagy-dependent degradation. DP significantly inhibits cell proliferation and enhances sensitivity to gemcitabine in pancreatic cancer cells. Mechanistically, CD147 inhibition upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) expression through H3K9 lactylation and suppresses the sterol regulatory element-binding protein 1 (SREBP1)/stearoyl-CoA desaturase-1 (SCD1) signaling pathway, collectively disrupting the balance of polyunsaturated and monounsaturated fatty acids, ultimately triggering ferroptosis. The combination of DP and gemcitabine demonstrates remarkable synergistic anti-tumor effects in orthotopic xenograft models, spontaneous KPC mouse models, and patient-derived organoid (PDO) and xenograft (PDX) models. In conclusion, this study reveals a mechanism by which CD147 regulates ferroptosis and supports combining DP with gemcitabine as a therapeutic strategy to improve patient outcomes in pancreatic ductal adenocarcinoma.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 8","pages":"102292"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944847","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-21DOI: 10.1016/j.xcrm.2025.102243
Junxiang Chen, Jin Li, Chunxi Zhang, Xinxin Zhi, Lei Wang, Quncheng Zhang, Pengfei Yu, Fei Tang, Xiankui Zha, Limin Wang, Wenrui Dai, Hongkai Xiong, Jiayuan Sun
{"title":"Deep learning for detection and diagnosis of intrathoracic lymphadenopathy from endobronchial ultrasound multimodal videos: A multi-center study.","authors":"Junxiang Chen, Jin Li, Chunxi Zhang, Xinxin Zhi, Lei Wang, Quncheng Zhang, Pengfei Yu, Fei Tang, Xiankui Zha, Limin Wang, Wenrui Dai, Hongkai Xiong, Jiayuan Sun","doi":"10.1016/j.xcrm.2025.102243","DOIUrl":"10.1016/j.xcrm.2025.102243","url":null,"abstract":"<p><p>Convex probe endobronchial ultrasound (CP-EBUS) ultrasonographic features are important for diagnosing intrathoracic lymphadenopathy. Conventional methods for CP-EBUS imaging analysis rely heavily on physician expertise. To overcome this obstacle, we propose a deep learning-aided diagnostic system (AI-CEMA) to automatically select representative images, identify lymph nodes (LNs), and differentiate benign from malignant LNs based on CP-EBUS multimodal videos. AI-CEMA is first trained using 1,006 LNs from a single center and validated with a retrospective study and then demonstrated with a prospective multi-center study on 267 LNs. AI-CEMA achieves an area under the curve (AUC) of 0.8490 (95% confidence interval [CI], 0.8000-0.8980), which is comparable to experienced experts (AUC, 0.7847 [95% CI, 0.7320-0.8373]; p = 0.080). Additionally, AI-CEMA is successfully transferred to a pulmonary lesion diagnosis task and obtains a commendable AUC of 0.8192 (95% CI, 0.7676-0.8709). In conclusion, AI-CEMA shows great potential in clinical diagnosis of intrathoracic lymphadenopathy and pulmonary lesions by providing automated, noninvasive, and expert-level diagnosis.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102243"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688994","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-23DOI: 10.1016/j.xcrm.2025.102246
Inês B Moreira, Charlotte Rossdam, Jonas Kaynert, Julia Beimdiek, Manuel M Vicente, Jessica Schmitz, Anika Großhennig, Astrid Oberbeck, Michèle J Hoffmann, Michele E Rosero Moreno, Daniel Steinbach, Maria L Barcena, Yannick Lippka, Jan H Bräsen, Hossein Tezval, Falk F R Buettner
{"title":"Neolactotetraosylceramide enables urinary detection of bladder cancer.","authors":"Inês B Moreira, Charlotte Rossdam, Jonas Kaynert, Julia Beimdiek, Manuel M Vicente, Jessica Schmitz, Anika Großhennig, Astrid Oberbeck, Michèle J Hoffmann, Michele E Rosero Moreno, Daniel Steinbach, Maria L Barcena, Yannick Lippka, Jan H Bräsen, Hossein Tezval, Falk F R Buettner","doi":"10.1016/j.xcrm.2025.102246","DOIUrl":"10.1016/j.xcrm.2025.102246","url":null,"abstract":"<p><p>Glycosphingolipids (GSLs) are promising cancer biomarkers. Using multiplexed capillary gel-electrophoresis with laser-induced fluorescence detection (xCGE-LIF), we profile GSLs in bladder cancer (BC) tissues and find a significant increase in neolactotetraosylceramide (nLc4) compared to matched normal tissue (n = 30). Immunofluorescence confirms tumor-specific nLc4 expression in both non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), colocalizing with luminal and basal urothelial markers. Analysis of paired tissue/urine samples, along with BC cell lines, reveals secretion of nLc4 associated with extracellular vesicles in MIBC. Urine profiling shows elevated nLc4 levels in BC patients (n = 16) versus controls (n = 50; area under the curve [AUC] 0.75; accuracy 82%). To support clinical translation, we apply an anti-nLc4 ELISA in a discovery cohort (n = 18) and a multi-center validation cohort (n = 123). In the validation set, urinary nLc4 levels are significantly elevated in MIBC (AUC 0.78; accuracy 64%) and increase with disease severity. These findings support the potential of urinary nLc4 as a non-invasive biomarker for BC detection.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102246"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706534","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":"Synergically enhanced anti-tumor immunity of in vivo panCAR by circRNA vaccine boosting.","authors":"Yanyan Wang, Liangru Lin, Xinyue Wang, Jing Li, Qian Pan, Haomeng Kou, Jie Yin, Fei Gao, Xinyuan Liao, Chenchen Zhang, Qimeng Yin, Chengzhi Zhao, Xinyang Li, Jinzhong Lin, Yichi Xu, Min Qiu, Dan Luo, Liang Qu","doi":"10.1016/j.xcrm.2025.102250","DOIUrl":"10.1016/j.xcrm.2025.102250","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies, but it still faces challenges, including high costs, a time-consuming manufacturing process, and the necessity of lymphodepletion. Here, we generate circular RNAs (circRNAs) encoding CAR proteins, referred to as circRNA<sup>CAR</sup>, which mediates remarkable tumor killing in human primary T cells. We demonstrate that circRNA<sup>CAR</sup>, delivered with immunocyte-tropic lipid nanoparticles (LNPs), can form in vivo panCAR cells (CAR-T, CAR-natural killer [NK], and CAR-macrophage), significantly inhibit tumor growth, and reshape the tumor microenvironment in mice. Importantly, combining in vivo panCAR with circRNA-based vaccines encoding the corresponding HER2 antigens exhibits synergistically enhanced anti-tumor immunity. Notably, circRNA<sup>CAR</sup> can in return boost the level of vaccination-elicited HER2-specific antibodies, mediating effective killing of tumor cells by macrophages. In combination with vaccination, in vivo panCAR demonstrates a synergistic enhancement of anti-tumor immunity across various mouse models, thereby establishing a framework for the synergistic in vivo panCAR-VAC immunotherapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102250"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717571","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-28DOI: 10.1016/j.xcrm.2025.102252
Mariana Pereira Pinho, Elie Antoun, Balraj Sandhar, Ting Shu, Fei Gao, Xiaobao Yang, Adam Bates, Lucia Cerundolo, Megat H B A Hamid, David Maldonado-Perez, Renuka Teague, Eve Warner, Lucinda Winter, Nasullah Khalid Alham, Clare Verrill, Simon R Lord, Timothy Rostron, Sally-Ann Clark, Craig Waugh, Paul Sopp, Chris Conlon, Ricardo A Fernandes, Adrian L Harris, Yanchun Peng, Asha Adwani, Tao Dong
{"title":"Tumor-specific CD8 T cell characterization in HR<sup>+</sup> breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.","authors":"Mariana Pereira Pinho, Elie Antoun, Balraj Sandhar, Ting Shu, Fei Gao, Xiaobao Yang, Adam Bates, Lucia Cerundolo, Megat H B A Hamid, David Maldonado-Perez, Renuka Teague, Eve Warner, Lucinda Winter, Nasullah Khalid Alham, Clare Verrill, Simon R Lord, Timothy Rostron, Sally-Ann Clark, Craig Waugh, Paul Sopp, Chris Conlon, Ricardo A Fernandes, Adrian L Harris, Yanchun Peng, Asha Adwani, Tao Dong","doi":"10.1016/j.xcrm.2025.102252","DOIUrl":"10.1016/j.xcrm.2025.102252","url":null,"abstract":"<p><p>Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR<sup>+</sup>) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR<sup>+</sup> breast cancer patients, especially those with early-stage tumors. When present, the circulating antitumor CD8 response contains cytotoxic T cells with diverse specificity and T cell receptor (TCR) repertoire. Additionally, patients with blood cancer-specific T cells have significantly more CD8 tumor-infiltrating lymphocytes (TILs). Moreover, tumor-reactive TCR sequences are detected in the tumor, but at a significantly lower proportion in patients with lymph node involvement. Our data suggest that HR<sup>+</sup> breast cancer patients with lymph node metastasis lack tumor-specific CD8 T cells with capacity to infiltrate the tumor at significant levels. However, early-stage patients have a diverse antitumor CD8 response that could be harnessed to develop immunotherapeutic approaches for late-stage HR<sup>+</sup> patients.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102252"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741325","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-31DOI: 10.1016/j.xcrm.2025.102262
Andrew D Hoffmann, Hannah Faisal Almubarak, Radhika Iyer, Sam E Weinberg, Joshua R Squires, Chengsheng Mao, Juncheng Wei, Shuvam Chaudhuri, Lamiaa El-Shennawy, Nurmaa K Dashzeveg, Yuzhi Jia, Alexis R Demonbreun, Matthew J Schipma, Yuan Luo, Suchitra Swaminathan, Michael G Ison, Huiping Liu, Deyu Fang
{"title":"Identification of immune signatures associated with both SARS-CoV-2 infection and lung transplantation.","authors":"Andrew D Hoffmann, Hannah Faisal Almubarak, Radhika Iyer, Sam E Weinberg, Joshua R Squires, Chengsheng Mao, Juncheng Wei, Shuvam Chaudhuri, Lamiaa El-Shennawy, Nurmaa K Dashzeveg, Yuzhi Jia, Alexis R Demonbreun, Matthew J Schipma, Yuan Luo, Suchitra Swaminathan, Michael G Ison, Huiping Liu, Deyu Fang","doi":"10.1016/j.xcrm.2025.102262","DOIUrl":"10.1016/j.xcrm.2025.102262","url":null,"abstract":"<p><p>Lung transplantation (lung-tx) offers the last life-saving option for patients with COVID-19-associated lung injury (CALI). We show that the RBD-specific antibodies are dramatically reduced in these CALI lung-tx patients despite a comparable frequency of CD19<sup>+</sup> B cells in circulating blood between CALI lung-tx patients and sero-negative controls. In contrast, non-transplant COVID-19 groups maintain a high level of RBD-specific antibodies. Single-cell RNA sequencing of white blood cells (WBCs) reveals three populations expanded in CALI lung-tx patients, including \"lung-tx CD14<sup>+</sup>FCGR3B(CD16b)<sup>+</sup> neutrophils,\" \"lung-tx CD8<sup>+</sup> T cells,\" and \"KLF2<sup>+</sup> CD4<sup>+</sup> T cells,\" alongside reduced conventional T and B lymphocytes. Elevated expression of interferon (IFN)-responsive genes as part of COVID-19 molecular signatures is sustained in some clusters of monocytes, Tregs, and B cells in all COVID-19 groups. Multiplex analysis of cytokines and chemokines detects a statistically significant increase in interleukin (IL)-6, IL-8, MCP-1, and MIP-1α in circulating blood, specifically in CALI lung-tx patients.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102262"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764635","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}
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