{"title":"GZR18, a GLP-1 analog with once-weekly or bi-weekly dosing for body weight management: A randomized, placebo-controlled, phase 1b/2a trial.","authors":"Linong Ji, Leili Gao, Ruihua Dong, Mingxia Yuan, Dong Zhao, Shuguang Pang, Jing Zhao, Liyuan Zhao, Wei Chen","doi":"10.1016/j.xcrm.2026.102743","DOIUrl":"10.1016/j.xcrm.2026.102743","url":null,"abstract":"<p><p>GZR18 is a glucagon-like peptide-1 receptor agonist under development for overweight/obesity. In this randomized, placebo-controlled phase 1b/2a trial in Chinese adults with overweight or obesity, different dose titration regimens and dosing frequencies (once-weekly [QW] vs. bi-weekly [Q2W]) are evaluated to assess safety and weight-loss efficacy over 26 weeks (Part A) or 35 weeks (Part B). Sixty participants are enrolled, of whom 46 complete the trial. The least-squares mean change in body weight is -9.36% for GZR18 vs. 6.68% for placebo in Part A and -17.8% (QW) and -12.8% (Q2W) for GZR18 vs. 0.7% for placebo in Part B; GZR18 also improves other weight-related and metabolic parameters. GZR18 is generally safe and well tolerated, with mostly mild-to-moderate gastrointestinal adverse events and no investigational-product-related serious adverse events reported. These findings warrant larger and longer trials of GZR18 for body weight management. The trial is registered at ClinicalTrials.gov (NCT06256536).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102743"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644048","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 : 2026-04-21Epub Date: 2026-03-26DOI: 10.1016/j.xcrm.2026.102703
John Gubatan, Raoul S Sojwal, Jiayu Ye, Theresa L Boye, Jacqueline N Hoang, Touran Fardeen, Michelle Temby, Samuel J S Rubin, Sean P Spencer, Prasanti Kotagiri, Stephan Rogalla, Michael J Rosen, Ole Haagen Nielsen, Scott Boyd, Justin Sonnenburg, Sidhartha R Sinha
{"title":"Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease.","authors":"John Gubatan, Raoul S Sojwal, Jiayu Ye, Theresa L Boye, Jacqueline N Hoang, Touran Fardeen, Michelle Temby, Samuel J S Rubin, Sean P Spencer, Prasanti Kotagiri, Stephan Rogalla, Michael J Rosen, Ole Haagen Nielsen, Scott Boyd, Justin Sonnenburg, Sidhartha R Sinha","doi":"10.1016/j.xcrm.2026.102703","DOIUrl":"10.1016/j.xcrm.2026.102703","url":null,"abstract":"<p><p>Loss of immune tolerance to the gut microbiome plays a pathogenic role in inflammatory bowel disease (IBD). How dietary factors alter host immune-gut microbiome interactions in IBD is unclear. Here, we apply multi-omics (immunoglobulin A or G and 16S rRNA sequencing [IgA-seq, IgG-seq], blood single-cell RNA sequencing [scRNA-seq], and immune repertoire sequencing) to investigate the effects of 12 weeks of vitamin D on host immune microbe interactions in patients with IBD. Vitamin D treatment associates with decreased disease activity and inflammatory markers and increased IgA-bound and decreased IgG-bound gut microbiota. Vitamin D alters the profiles of IgA-bound (increased Lachnospiraceae, Blautia) and IgG-bound (decreased Proteobacteria, Enterococcaceae) gut bacteria. Vitamin D increases B cell activating factor (BAFF) signaling between plasmacytoid dendritic cells and B cells, alters BCR and TCR clonotypes that associate with Ig-bound gut microbiota, and increases α4β7+ B and T regulatory cells. Our results demonstrate that vitamin D promotes immune tolerance to gut microbiota in patients with IBD. Clinical trial is registered under NCT04828031.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102703"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527249","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 : 2026-04-21Epub Date: 2026-03-24DOI: 10.1016/j.xcrm.2026.102693
Hung-Jen Chen, Brent Appelman, Hanneke L D M Willemen, Amelie Bos, Judith Prado, W Ashwin Mak, Noa Keijzer, Patrícia Silva Santos Ribeiro, Sara Vieira Goncalves, Sabine Versteeg, Chiara E Geyer, Mads Larsen, Eline Schüchner, Marije K Bomers, Ayesha H A Lavell, Braeden Charlton, Rob Wüst, W Joost Wiersinga, Michèle van Vugt, Gestur Vidarsson, Niels Eijkelkamp, Jeroen den Dunnen
{"title":"Transfer of IgG from long COVID patients induces symptomology in mice.","authors":"Hung-Jen Chen, Brent Appelman, Hanneke L D M Willemen, Amelie Bos, Judith Prado, W Ashwin Mak, Noa Keijzer, Patrícia Silva Santos Ribeiro, Sara Vieira Goncalves, Sabine Versteeg, Chiara E Geyer, Mads Larsen, Eline Schüchner, Marije K Bomers, Ayesha H A Lavell, Braeden Charlton, Rob Wüst, W Joost Wiersinga, Michèle van Vugt, Gestur Vidarsson, Niels Eijkelkamp, Jeroen den Dunnen","doi":"10.1016/j.xcrm.2026.102693","DOIUrl":"10.1016/j.xcrm.2026.102693","url":null,"abstract":"<p><p>SARS-CoV-2 infections have led to a surge in long COVID, a post-infectious syndrome in which autoantibodies are proposed to play a pathogenic role, analogous to fibromyalgia. Here, we test this hypothesis by transferring total IgG from long COVID patients into mice. We stratified patients into three subgroups using plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and interferon-β, with subgroup-specific pathways supported by plasma proteomics. Transfer of pooled total IgG induces pronounced and persistent mechanical hypersensitivity. Notably, IgG collected 2 years later from the same long COVID patients who remained symptomatic reproduced mechanical allodynia in mice, demonstrating longitudinal stability of pathogenic activity. Proteome-wide autoantibody profiling identifies elevated, subgroup-linked autoreactivities that persist over time and are validated by independent assays. Together, these findings demonstrate that long COVID IgG can induce mechanical hypersensitivity in mice, support a causal role for autoantibodies in long COVID pathogenesis, and may establish a murine model for therapeutic development.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102693"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510159","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 : 2026-04-21Epub Date: 2026-03-30DOI: 10.1016/j.xcrm.2026.102701
Rex L Hung, Wilson W Ng, Peter K C Chung, Ashley B S Li, Theodora H Y Luk, Rosanna Fong, Anna Lee, Raina Mok, Hebronson Yung, Vera Tse, Raven Cheng, Amandine Schneider, Rachel L Telford, Florian Dubois, Elsa Bourayou, Rafael De Andrade Moral, Jean-Marc Doisne, Milena Hasan, Gabriel M Leung, Michael Y Ni, Michael Tse, Malik Peiris, James P Di Santo, Roberto Bruzzone, Vincent Rouilly, Darragh Duffy
{"title":"The healthy human global project - Hong Kong: A community-based cross-sectional study of a healthy Asian population.","authors":"Rex L Hung, Wilson W Ng, Peter K C Chung, Ashley B S Li, Theodora H Y Luk, Rosanna Fong, Anna Lee, Raina Mok, Hebronson Yung, Vera Tse, Raven Cheng, Amandine Schneider, Rachel L Telford, Florian Dubois, Elsa Bourayou, Rafael De Andrade Moral, Jean-Marc Doisne, Milena Hasan, Gabriel M Leung, Michael Y Ni, Michael Tse, Malik Peiris, James P Di Santo, Roberto Bruzzone, Vincent Rouilly, Darragh Duffy","doi":"10.1016/j.xcrm.2026.102701","DOIUrl":"10.1016/j.xcrm.2026.102701","url":null,"abstract":"<p><p>Immune responses vary between individuals due to age, sex, genetics, and environment, yet most systems immunology studies focus on populations of European ancestry. To address this gap, we established the Healthy Human Global Project - Hong Kong (HHGP-HK) to characterize immune variability in a healthy Asian population. Modeled on the French Milieu Intérieur study, we adapted inclusion and exclusion criteria and collected harmonized demographic, medical, and lifestyle data for cross-cohort comparisons. We observed significant age- and sex-associated differences across multiple clinical laboratory measures, mirroring findings from Milieu Intérieur, with notable exceptions for C-reactive protein and liver enzymes that may reflect environmental differences. Application of biological aging, physiological, and mental health scores highlighted limitations of existing metrics in non-European populations. Wearable fitness trackers further revealed age- and sex-related differences in sleep, physical activity, and heart rate variability. The HHGP-HK cohort provides a valuable resource for understanding immune variability in Asian populations.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102701"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590383","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 : 2026-04-21Epub Date: 2026-03-31DOI: 10.1016/j.xcrm.2026.102722
Yao Yu Yeo, Huaying Qiu, Yunhao Bai, Bokai Zhu, Yuzhou Chang, Fabio Iannelli, Stephanie Pei Tung Yiu, Jason Yeung, Hendrik A Michel, Yuchen Wang, Yang Wang, Wenrui Wu, Kyle Wright, Muhammad Shaban, Sam Sadigh, Dingani Nkosi, Vignesh Shanmugam, Philip Rock, Precious Cramer, Julia Paczkowska, Pierre Stephan, Guanrui Liao, Amy Y Huang, Hongbo Wang, Han Chen, Leonie Frauenfeld, Louisa Kaufmann, Stefano Pileri, Bidisha Mitra, Benjamin E Gewurz, Bo Zhao, Garry P Nolan, Baochun Zhang, Alex K Shalek, Michael Angelo, Christian M Schürch, Faisal Mahmood, Roberto Chiarle, Qin Ma, W Richard Burack, Margaret A Shipp, Scott J Rodig, Sizun Jiang
{"title":"Epstein-Barr virus orchestrates spatial reorganization and immunomodulation in the classic Hodgkin lymphoma tumor microenvironment.","authors":"Yao Yu Yeo, Huaying Qiu, Yunhao Bai, Bokai Zhu, Yuzhou Chang, Fabio Iannelli, Stephanie Pei Tung Yiu, Jason Yeung, Hendrik A Michel, Yuchen Wang, Yang Wang, Wenrui Wu, Kyle Wright, Muhammad Shaban, Sam Sadigh, Dingani Nkosi, Vignesh Shanmugam, Philip Rock, Precious Cramer, Julia Paczkowska, Pierre Stephan, Guanrui Liao, Amy Y Huang, Hongbo Wang, Han Chen, Leonie Frauenfeld, Louisa Kaufmann, Stefano Pileri, Bidisha Mitra, Benjamin E Gewurz, Bo Zhao, Garry P Nolan, Baochun Zhang, Alex K Shalek, Michael Angelo, Christian M Schürch, Faisal Mahmood, Roberto Chiarle, Qin Ma, W Richard Burack, Margaret A Shipp, Scott J Rodig, Sizun Jiang","doi":"10.1016/j.xcrm.2026.102722","DOIUrl":"10.1016/j.xcrm.2026.102722","url":null,"abstract":"<p><p>Classic Hodgkin lymphoma (cHL) is composed of rare malignant Hodgkin and Reed-Sternberg (HRS) cells within a T-cell-rich tumor microenvironment (TME). Epstein-Barr virus (EBV) is present in ∼25% of cases, but its contribution to pathogenesis and immunomodulation remains unclear due to technical barriers. Using complementary spatial proteomics and transcriptomics across multi-institutional cohorts, we systematically map key EBV-linked TME reorganization. EBV-positive cHL exhibits distinct immunological features, including memory CD8 T cell enrichment, heightened T cell dysfunction spatially correlated with HRS proximity, and terminally exhausted T cell signatures contrasting with progenitor-exhausted patterns in EBV-negative disease. We identify EBV-encoded LMP1 as a factor in T cell dysfunction through enhanced HRS:CD8 interactions, and its expression level correlates with T cell terminal exhaustion in a distance-dependent manner. This spatial framework dissects viral-mediated immune evasion in the cHL TME, highlighting potential therapeutic opportunities to target virus-associated T cell dysfunction for precision immunotherapy in virus-associated malignancies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102722"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589965","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 the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.","authors":"Juan Liu, Weiwei Wang, Yvonne Sun, Shan Huang, Arnav Borole, Haiyan Zheng, Wenwei Hu, Zhaohui Feng","doi":"10.1016/j.xcrm.2026.102704","DOIUrl":"10.1016/j.xcrm.2026.102704","url":null,"abstract":"<p><p>Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine synthesis, is frequently overexpressed in cancers and promotes cancer progression. Its oncogenic role has been largely attributed to its enzymatic activity. Here, we uncover a critical noncanonical function of PHGDH in cancer; PHGDH upregulates PD-L1 expression to promote cancer immune evasion independently of its enzymatic function. Mechanistically, PHGDH binds to the serine/threonine kinase RAF1 and disrupts its interaction with 14-3-3, thereby activating RAF1 and its downstream MEK/ERK signaling to induce PD-L1 expression. Elevated PHGDH levels correlate with increased PD-L1 expression in clinical tumor samples. In preclinical mouse models, tumors with high PHGDH expression exhibit increased sensitivity to PD-1/PD-L1 blockade. Combining PHGDH inhibitors with PD-1/PD-L1 blockade significantly improves antitumor effects compared to individual treatments. These results identify PHGDH as an important PD-L1 regulator, reveal a critical noncanonical mechanism underlying PHGDH's oncogenic function, and propose a potential therapeutic strategy for cancers with PHGDH overexpression.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102704"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572634","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 : 2026-04-21Epub Date: 2026-04-10DOI: 10.1016/j.xcrm.2026.102741
Zhuo Wang, Qing Luo, Jie Wu, Li Lu, Wenjie Ding, Yichun Zhao, Yongfeng Yu, Ruoran Qiu, Ling Zhu, Xinxing Ouyang, Wendi Xuzhang, Shun Lu, Wei Wei, Qihui Shi, Ziming Li
{"title":"Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.","authors":"Zhuo Wang, Qing Luo, Jie Wu, Li Lu, Wenjie Ding, Yichun Zhao, Yongfeng Yu, Ruoran Qiu, Ling Zhu, Xinxing Ouyang, Wendi Xuzhang, Shun Lu, Wei Wei, Qihui Shi, Ziming Li","doi":"10.1016/j.xcrm.2026.102741","DOIUrl":"10.1016/j.xcrm.2026.102741","url":null,"abstract":"<p><p>Combined small-cell lung cancer (cSCLC) is an aggressive subtype of SCLC with mixed histologic components. Despite heterogeneity and poorer prognosis than de novo SCLC, cSCLC is managed as SCLC because molecular insight into biology, lineage plasticity, and tumor microenvironment (TME) is limited. We perform spatial whole-exome sequencing, spatial transcriptomics, and single-nucleus RNA sequencing across 19 treatment-naive cSCLC tumors. Different histologic components share a monoclonal origin, whereas divergence associates with distinct mutation and copy-number alteration patterns. Our results define spatially exclusive or interspersed tumor domains with distinct TME and immune landscapes; fibroblast-rich boundaries enriched for an aggressive fibroblast subtype may shape TME and treatment responses. We identify lineage plasticity, including adenocarcinoma-to-SCLC transdifferentiation and SCLC-subtype coexistence, and develop cSCLC Detector, a sensitive mutation-based assay improving cSCLC detection in tissue and liquid biopsies. These findings illuminate cSCLC evolution and heterogeneity, underscoring the need for tailored diagnostic and therapeutic strategies for this aggressive subtype.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102741"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662305","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 : 2026-04-21Epub Date: 2026-03-26DOI: 10.1016/j.xcrm.2026.102699
Yanqin Liu, Jiliang Zhao, Kailu Yang, Qiongqiong Ma, Dongping Zhang, Lili Xu, Zhaoyuan Zhang, Zhongqian Yin, Jingru Chen, Yi Wang, Han Wang, Feilong Zhou, Minghui Han, Jie Wang, Fan Li, Yanqin Xu, Yi Yang, Wei Wang, Spencer Huggett, Alexander Chung, Jinping Gan, Bo Zhang, Ziying Zhou, Youjia Cao, Dan Ding, Meiyun Wang, Hongkai Zhang
{"title":"Immunogenic tumor cell death and T-cell-derived IFN-γ elicit tumoricidal macrophages to potentiate OX40 immunotherapy.","authors":"Yanqin Liu, Jiliang Zhao, Kailu Yang, Qiongqiong Ma, Dongping Zhang, Lili Xu, Zhaoyuan Zhang, Zhongqian Yin, Jingru Chen, Yi Wang, Han Wang, Feilong Zhou, Minghui Han, Jie Wang, Fan Li, Yanqin Xu, Yi Yang, Wei Wang, Spencer Huggett, Alexander Chung, Jinping Gan, Bo Zhang, Ziying Zhou, Youjia Cao, Dan Ding, Meiyun Wang, Hongkai Zhang","doi":"10.1016/j.xcrm.2026.102699","DOIUrl":"10.1016/j.xcrm.2026.102699","url":null,"abstract":"<p><p>Understanding the mechanisms limiting OX40 agonist antibody efficacy is critical for developing more effective combination immunotherapies. Tumor microenvironment (TME) analysis revealed that OX40-antibody-responsive mice harbored tumor-associated macrophages (TAMs) with elevated NOS2 expression and heightened pattern recognition receptor (PRR) activation and interferon gamma (IFN-γ) signaling. In addition, patients with more favorable treatment responses to OX40 antibody therapy exhibited increased NOS2 expression. Mechanistically, tumor-infiltrating T-cell-derived IFN-γ synergizes with endogenous ligands of PRR released during immunogenic cell death to drive NOS2<sup>+</sup> TAMs reprogramming. Translating these insights into therapeutic strategy, a Combo approach composing of MPLA, IFN-γ, and OX40 agonist antibody is designed to actively polarize TAMs to express NOS2, which mediate tumor clearance through an NOS2-dependent cytotoxicity. Moreover, OX40-antibody-mediated regulatory T cell (Treg) depletion potentiated NOS2<sup>+</sup> macrophage induction. This multimodal strategy offers a promising solution to overcome the limitations of OX40 antibody monotherapy and enhance outcomes of the OX40-targeted immunotherapies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102699"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527266","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 : 2026-04-21Epub Date: 2026-03-30DOI: 10.1016/j.xcrm.2026.102713
Zicheng Zhang, Dongfang Wu, Ruanqi Chen, Modi Zhai, Fan Yang, Jiaqian Wang, Lei Guo, Li Liu, Jianming Ying, Lin Yang, Meng Zhou
{"title":"Single-cell spatial transcriptomics reveals tumor microenvironment heterogeneity in primary and lymph node-metastatic small cell lung cancer.","authors":"Zicheng Zhang, Dongfang Wu, Ruanqi Chen, Modi Zhai, Fan Yang, Jiaqian Wang, Lei Guo, Li Liu, Jianming Ying, Lin Yang, Meng Zhou","doi":"10.1016/j.xcrm.2026.102713","DOIUrl":"10.1016/j.xcrm.2026.102713","url":null,"abstract":"<p><p>Lymph node metastasis (LNM) is a critical prognostic and therapeutic determinant in small cell lung cancer (SCLC), yet its spatial cellular ecosystem remains poorly understood. Here, we perform single-cell spatial transcriptomics using the CosMx Spatial Molecular Imager on 105 primary and metastatic lymph node specimens from 75 SCLC patients, generating a comprehensive atlas of over 600,000 cells. We identify three LNM-enriched malignant subclusters with distinct metabolic and angiogenic programs that spatially correlate with immune exclusion features. Spatial analysis reveals vascular-immune crosstalk, wherein endothelial cells orchestrate immune activation through avoidance of malignant cells while forming functional perivascular niches with cytotoxic T cells during LNM. Cellular neighborhood analysis delineates distinct multicellular niches and identifies a pan-immune hotspot (PIHs-1) whose abundance is an independent predictor of survival. This study provides a high-resolution spatial map of the SCLC tumor microenvironment during LNM and establishes spatially defined architectures as both mechanistic insights and translatable biomarkers.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102713"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590339","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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