GastroenterologyPub Date : 2026-05-06DOI: 10.1053/j.gastro.2026.04.021
Larissa Belz, Dominic van den Heuvel, Badr Kilani, Alejandro Martinez-Navarro, Anastassia Akhalkatsi, Markus Joppich, Yinfeng Zhu, Qiongjie Ding, Jinlong Wan, Julia Stermann, Julia Winterhalter, Denise Messerer, Anna Titova, Sanjana Balaji, Santoshi Giri, Luke Eivers, Sebastian Widholz, Stefanie Bärthel, Elisabeth Raatz, Dieter Saur, Kirsten Lauber, Georg Beyer, Julia Mayerle, Steffen Ormanns, Michael Guenther, Steffen Massberg, Hellen Ishikawa-Ankerhold, Konstantin Stark
{"title":"Neutrophil-Driven Trogocytosis in PDAC Liver Metastases Restrains Immunosuppressive Macrophage Polarization and Limits Metastatic Progression.","authors":"Larissa Belz, Dominic van den Heuvel, Badr Kilani, Alejandro Martinez-Navarro, Anastassia Akhalkatsi, Markus Joppich, Yinfeng Zhu, Qiongjie Ding, Jinlong Wan, Julia Stermann, Julia Winterhalter, Denise Messerer, Anna Titova, Sanjana Balaji, Santoshi Giri, Luke Eivers, Sebastian Widholz, Stefanie Bärthel, Elisabeth Raatz, Dieter Saur, Kirsten Lauber, Georg Beyer, Julia Mayerle, Steffen Ormanns, Michael Guenther, Steffen Massberg, Hellen Ishikawa-Ankerhold, Konstantin Stark","doi":"10.1053/j.gastro.2026.04.021","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.04.021","url":null,"abstract":"<p><strong>Background & aims: </strong>Pancreatic Ductal Adenocarcinoma (PDAC) metastasizes early and frequently to the liver, limiting therapeutic options and resulting in poor prognosis. Neutrophils are key immune players in cancer progression, yet their role in PDAC liver metastases remains unclear. This study investigates how neutrophils influence hepatic macrophages and modulate the immune landscape in the metastatic microenvironment using intravital calcium imaging and single-cell RNA sequencing (scRNA-seq).</p><p><strong>Methods: </strong>Intravital microscopy was used to monitor neutrophil behavior and interactions within the metastatic niche. We employed intravital calcium imaging in LysMcre-PCG5-tdt mice to visualize real-time immune cell interactions and their functional impact in a PDAC metastasis model. To dissect the effect of neutrophils on the immune landscape, we performed single-cell RNA sequencing of liver-infiltrating leukocytes in tumor-bearing mice.</p><p><strong>Results: </strong>Intravital calcium imaging revealed that neutrophils are recruited to hepatic metastases by CCL2/CCL5, where they take up tumor cell fragments via trogocytosis and subsequently present these tumor fragments to hepatic macrophages. This neutrophil-driven immunomodulation was abolished upon neutrophil depletion, resulting in a permissive tumor-promoting macrophage phenotype. Single-cell RNA sequencing identified distinct macrophage subpopulations, demonstrating that neutrophils suppress the development of immunosuppressive macrophages by C3-dependent signaling and enhance anti-tumor signaling pathways.</p><p><strong>Conclusions: </strong>This study provides in vivo evidence of neutrophil-macrophage crosstalk in PDAC liver metastases and highlights the functional consequences of neutrophil depletion. By integrating intravital calcium imaging with single-cell RNA sequencing, we uncover a previously unrecognized mechanism of neutrophil-driven immunomodulation, emphasizing the potential for therapeutic strategies targeting neutrophil-macrophage interactions in metastatic PDAC.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856164","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}
GastroenterologyPub Date : 2026-05-05DOI: 10.1053/j.gastro.2026.04.030
Daniel Kotlarz
{"title":"Learning from CAR T-Cell Therapy in Pediatric Autoimmunity: Potential Applications for Gastroenterology.","authors":"Daniel Kotlarz","doi":"10.1053/j.gastro.2026.04.030","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.04.030","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836741","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}
GastroenterologyPub Date : 2026-05-05DOI: 10.1053/j.gastro.2026.04.033
Roos E Pouw, Lodewijk A A Brosens, Stella Mook, Nadia Haj Mohammad, Jelle P Ruurda, Bas L A M Weusten
{"title":"A 64-year-old patient with T1b esophageal adenocarcinoma: what treatment options do we have?","authors":"Roos E Pouw, Lodewijk A A Brosens, Stella Mook, Nadia Haj Mohammad, Jelle P Ruurda, Bas L A M Weusten","doi":"10.1053/j.gastro.2026.04.033","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.04.033","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836743","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}
GastroenterologyPub Date : 2026-05-02DOI: 10.1053/j.gastro.2026.04.028
Hicham Bouchiba, Barbara A J Bastiaansen, Evelien Dekker
{"title":"An unusual biliary manifestation in a patient with familial adenomatous polyposis: What is your diagnosis?","authors":"Hicham Bouchiba, Barbara A J Bastiaansen, Evelien Dekker","doi":"10.1053/j.gastro.2026.04.028","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.04.028","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836666","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}
GastroenterologyPub Date : 2026-05-01DOI: 10.1016/S0016-5085(26)00366-5
Mark M. Aloysius, Ahmad Nawaz, Ali Asad, Ganesh Aswath, Noam Peleg, Kelita Singh, Bishnu Sapkota
{"title":"3 VASOPRESSOR-INDEXED TIMING OF ERCP AND SURVIVAL IN SEPTIC SHOCK FROM TOKYO GRADE III CHOLANGITIS","authors":"Mark M. Aloysius, Ahmad Nawaz, Ali Asad, Ganesh Aswath, Noam Peleg, Kelita Singh, Bishnu Sapkota","doi":"10.1016/S0016-5085(26)00366-5","DOIUrl":"10.1016/S0016-5085(26)00366-5","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"170 6","pages":"Pages S-1-S-2"},"PeriodicalIF":25.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147756717","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}
GastroenterologyPub Date : 2026-05-01DOI: 10.1016/S0016-5085(26)00377-X
Rupa S. Kanchi, Kathleen Loomes, Keith Hazleton, Juliet Emamaullee, Kasper Wang, Pamela Valentino, Ronald J. Sokol, Phillip Rosenthal, Jean P Molleston, Alexander Miethke, John Magee, M. Kyle Jensen, Alyssa Kriegermeier, Saul J. Karpen, Simon Horslen, Arianna Barbetta, Cristian Coarfa, Benjamin Shneider
{"title":"156 THE PLASMA PROTEOME REVEALS PROGNOSTICALLY IMPORTANT MOLECULAR ENDOTYPES IN PEDIATRIC CHOLESTASIS","authors":"Rupa S. Kanchi, Kathleen Loomes, Keith Hazleton, Juliet Emamaullee, Kasper Wang, Pamela Valentino, Ronald J. Sokol, Phillip Rosenthal, Jean P Molleston, Alexander Miethke, John Magee, M. Kyle Jensen, Alyssa Kriegermeier, Saul J. Karpen, Simon Horslen, Arianna Barbetta, Cristian Coarfa, Benjamin Shneider","doi":"10.1016/S0016-5085(26)00377-X","DOIUrl":"10.1016/S0016-5085(26)00377-X","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"170 6","pages":"Pages S-6-S-7"},"PeriodicalIF":25.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147756727","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}