Journal of Experimental Medicine最新文献_第9页

Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile. 产生琥珀酸的微生物群促使簇细胞增生以抵御艰难梭菌。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-01-06 Epub Date: 2024-11-26 DOI: 10.1084/jem.20232055

Tasia D Kellogg, Simona Ceglia, Benedikt M Mortzfeld, Tanvi M Tanna, Abigail L Zeamer, Matthew R Mancini, Sage E Foley, Doyle V Ward, Shakti K Bhattarai, Beth A McCormick, Andrea Reboldi, Vanni Bucci

{"title":"Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.","authors":"Tasia D Kellogg, Simona Ceglia, Benedikt M Mortzfeld, Tanvi M Tanna, Abigail L Zeamer, Matthew R Mancini, Sage E Foley, Doyle V Ward, Shakti K Bhattarai, Beth A McCormick, Andrea Reboldi, Vanni Bucci","doi":"10.1084/jem.20232055","DOIUrl":"10.1084/jem.20232055","url":null,"abstract":"The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716370","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}

引用次数: 0

MAIT cells: Conserved watchers on the wall. MAIT 细胞：墙壁上的守望者

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-01-06 Epub Date: 2024-10-24 DOI: 10.1084/jem.20232298

Lilou Germain, Pablo Veloso, Olivier Lantz, François Legoux

{"title":"MAIT cells: Conserved watchers on the wall.","authors":"Lilou Germain, Pablo Veloso, Olivier Lantz, François Legoux","doi":"10.1084/jem.20232298","DOIUrl":"10.1084/jem.20232298","url":null,"abstract":"MAIT cells are innate-like T cells residing in barrier tissues such as the lung, skin, and intestine. Both the semi-invariant T cell receptor of MAIT cells and the restricting element MR1 are deeply conserved across mammals, indicating non-redundant functions linked to antigenic specificity. MAIT cells across species concomitantly express cytotoxicity and tissue-repair genes, suggesting versatile functions. Accordingly, MAIT cells contribute to antibacterial responses as well as to the repair of damaged barrier tissues. MAIT cells recognize riboflavin biosynthetic pathway-derived metabolites, which rapidly cross epithelial barriers to be presented by antigen-presenting cells. Changes in gut ecology during intestinal inflammation drive the expansion of strong riboflavin and MAIT ligand producers. Thus, MAIT cells may enable real-time surveillance of microbiota dysbiosis across intact epithelia and provide rapid and context-dependent responses. Here, we discuss recent findings regarding the origin and regulation of MAIT ligands and the role of MAIT cells in barrier tissues. We speculate on the potential reasons for MAIT cell conservation during evolution.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501659","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}

引用次数: 0

Bridging the gap between tumor and disease: Innovating cancer and glioma models. 弥合肿瘤和疾病之间的鸿沟：创新癌症和胶质瘤模型。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-01-06 Epub Date: 2024-12-03 DOI: 10.1084/jem.20220808

Stefano M Cirigliano, Howard A Fine

引用次数: 0

An unconventional purine connection. 非传统的嘌呤联系

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-19 DOI: 10.1084/jem.20241527

Fabio Grassi

引用次数: 0

Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease. 平衡状态和炎症性肠病中肠道 IgA 亚类的免疫分子和反应性景观

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-19 DOI: 10.1084/jem.20230079

Sonia Tejedor Vaquero, Hadas Neuman, Laura Comerma, Xavi Marcos-Fa, Celia Corral-Vazquez, Mathieu Uzzan, Marc Pybus, Daniel Segura-Garzón, Joana Guerra, Lisa Perruzza, Roser Tachó-Piñot, Jordi Sintes, Adam Rosenstein, Emilie K Grasset, Mar Iglesias, Monica Gonzalez Farré, Joan Lop, Maria Evangelina Patriaca-Amiano, Monica Larrubia-Loring, Pablo Santiago-Diaz, Júlia Perera-Bel, Pau Berenguer-Molins, Monica Martinez Gallo, Andrea Martin-Nalda, Encarna Varela, Marta Garrido-Pontnou, Fabio Grassi, Francisco Guarner, Saurabh Mehandru, Lucia Márquez-Mosquera, Ramit Mehr, Andrea Cerutti, Giuliana Magri

{"title":"Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease.","authors":"Sonia Tejedor Vaquero, Hadas Neuman, Laura Comerma, Xavi Marcos-Fa, Celia Corral-Vazquez, Mathieu Uzzan, Marc Pybus, Daniel Segura-Garzón, Joana Guerra, Lisa Perruzza, Roser Tachó-Piñot, Jordi Sintes, Adam Rosenstein, Emilie K Grasset, Mar Iglesias, Monica Gonzalez Farré, Joan Lop, Maria Evangelina Patriaca-Amiano, Monica Larrubia-Loring, Pablo Santiago-Diaz, Júlia Perera-Bel, Pau Berenguer-Molins, Monica Martinez Gallo, Andrea Martin-Nalda, Encarna Varela, Marta Garrido-Pontnou, Fabio Grassi, Francisco Guarner, Saurabh Mehandru, Lucia Márquez-Mosquera, Ramit Mehr, Andrea Cerutti, Giuliana Magri","doi":"10.1084/jem.20230079","DOIUrl":"10.1084/jem.20230079","url":null,"abstract":"The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function, and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19- PC subsets, respectively. IgA2+ PCs were extensively clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors. Of note, secretory IgA1 (SIgA1) and SIgA2 dually coated a large fraction of mucus-embedded bacteria, including Akkermansia muciniphila. Disruption of homeostasis by inflammatory bowel disease (IBD) was associated with an increase in actively proliferating IgA1+ plasmablasts, a depletion in long-lived IgA2+ PCs, and increased SIgA1+SIgA2+ gut microbiota. Such increase featured enhanced IgA1 reactivity to pathobionts, including Escherichia coli, combined with depletion of beneficial A. muciniphila. Thus, gut IgA1 and IgA2 emerge from clonally related PCs and show unique changes in both frequency and reactivity in IBD.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668013","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}

引用次数: 0

Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue. 白细胞介素-33 激活的嗜碱性粒细胞通过调节 Th2 细胞进入肺组织来促进哮喘的发生。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-09-19 DOI: 10.1084/jem.20240103

Martijn J Schuijs, Claudia M Brenis Gomez, Fabian Bick, Justine Van Moorleghem, Manon Vanheerswynghels, Geert van Loo, Rudi Beyaert, David Voehringer, Richard M Locksley, Hamida Hammad, Bart N Lambrecht

{"title":"Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue.","authors":"Martijn J Schuijs, Claudia M Brenis Gomez, Fabian Bick, Justine Van Moorleghem, Manon Vanheerswynghels, Geert van Loo, Rudi Beyaert, David Voehringer, Richard M Locksley, Hamida Hammad, Bart N Lambrecht","doi":"10.1084/jem.20240103","DOIUrl":"10.1084/jem.20240103","url":null,"abstract":"Asthma is characterized by lung eosinophilia, remodeling, and mucus plugging, controlled by adaptive Th2 effector cells secreting IL-4, IL-5, and IL-13. Inhaled house dust mite (HDM) causes the release of barrier epithelial cytokines that activate various innate immune cells like DCs and basophils that can promote Th2 adaptive immunity directly or indirectly. Here, we show that basophils play a crucial role in the development of type 2 immunity and eosinophilic inflammation, mucus production, and bronchial hyperreactivity in response to HDM inhalation in C57Bl/6 mice. Interestingly, conditional depletion of basophils during sensitization did not reduce Th2 priming or asthma inception, whereas depletion during allergen challenge did. During the challenge of sensitized mice, basophil-intrinsic IL-33/ST2 signaling, and not FcεRI engagement, promoted basophil IL-4 production and subsequent Th2 cell recruitment to the lungs via vascular integrin expression. Basophil-intrinsic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced key asthma features. Thus, IL-33-activated basophils are gatekeepers that boost allergic airway inflammation by controlling Th2 tissue entry.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288979","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}

引用次数: 0

The protozoan commensal Tritrichomonas musculis is a natural adjuvant for mucosal IgA. 原生动物共生体肌肉三联单胞菌是粘膜 IgA 的天然佐剂。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-13 DOI: 10.1084/jem.20221727

Eric Yixiao Cao, Kyle Burrows, Pailin Chiaranunt, Ana Popovic, Xueyang Zhou, Cong Xie, Ayushi Thakur, Graham Britton, Matthew Spindler, Louis Ngai, Siu Ling Tai, Dragos Cristian Dasoveanu, Albert Nguyen, Jeremiah J Faith, John Parkinson, Jennifer L Gommerman, Arthur Mortha

{"title":"The protozoan commensal Tritrichomonas musculis is a natural adjuvant for mucosal IgA.","authors":"Eric Yixiao Cao, Kyle Burrows, Pailin Chiaranunt, Ana Popovic, Xueyang Zhou, Cong Xie, Ayushi Thakur, Graham Britton, Matthew Spindler, Louis Ngai, Siu Ling Tai, Dragos Cristian Dasoveanu, Albert Nguyen, Jeremiah J Faith, John Parkinson, Jennifer L Gommerman, Arthur Mortha","doi":"10.1084/jem.20221727","DOIUrl":"10.1084/jem.20221727","url":null,"abstract":"Immunoglobulin (Ig) A supports mucosal immune homeostasis and host-microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial commensal microbes in the induction of IgA remains elusive. Here, we demonstrate that permanent colonization with the protozoan commensal Tritrichomonas musculis (T.mu) promotes T cell-dependent, IgA class-switch recombination, and intestinal accumulation of IgA-secreting plasma cells (PC). T.mu colonization specifically drives the expansion of T follicular helper cells and a unique ICOS+ non-Tfh cell population, accompanied by an increase in germinal center B cells. Blockade of ICOS:ICOSL co-stimulation or MHCII-expression on B cells is central for the induction of IgA following colonization by T.mu, implicating a previously underappreciated mode of IgA induction following protozoan commensal colonization. Finally, T.mu further improves the induction of IgA-secreting PC specific to orally ingested antigens and their peripheral dissemination, identifying T.mu as a \"natural adjuvant\" for IgA. Collectively, these findings propose a protozoa-driven mode of IgA induction to support intestinal immune homeostasis.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621251","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}

引用次数: 0

Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy. 缺乏 MHC-II 的小鼠对黑色素瘤的抑制：癌症免疫疗法的机制和意义。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-10-29 DOI: 10.1084/jem.20240797

Hexin Shi, Dawson Medler, Jianhui Wang, Rachel Browning, Aijie Liu, Sara Schneider, Claudia Duran Bojorquez, Ashwani Kumar, Xiaohong Li, Jiexia Quan, Sara Ludwig, James J Moresco, Chao Xing, Eva Marie Y Moresco, Bruce Beutler

{"title":"Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy.","authors":"Hexin Shi, Dawson Medler, Jianhui Wang, Rachel Browning, Aijie Liu, Sara Schneider, Claudia Duran Bojorquez, Ashwani Kumar, Xiaohong Li, Jiexia Quan, Sara Ludwig, James J Moresco, Chao Xing, Eva Marie Y Moresco, Bruce Beutler","doi":"10.1084/jem.20240797","DOIUrl":"10.1084/jem.20240797","url":null,"abstract":"Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II α chain, and its absence in C57BL/6J mice eliminates all MHC-II expression. H2-Aa deficiency, specifically in dendritic cells (DC), led to a quantitative increase in type 2 conventional DC (cDC2) and a decrease in cDC1. H2-Aa-deficient cDC2, but not cDC1, were essential for melanoma suppression and effectively cross-primed and recruited CD8 T cells into tumors. Lack of T regulatory cells, also observed in H2-Aa deficiency, contributed to melanoma suppression. Acute disruption of H2-Aa was therapeutic in melanoma-bearing mice, particularly when combined with checkpoint inhibition, which had no therapeutic effect by itself. Our findings suggest that inhibiting MHC-II may be an effective immunotherapeutic approach to enhance immune responses to cancer.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521984","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}

引用次数: 0

Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease. 严重波瓦桑、乌苏图或罗斯河病毒病患者体内中和 I 型 IFN 的自身抗体。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-01 DOI: 10.1084/jem.20240942

Adrian Gervais, Paul Bastard, Lucy Bizien, Céline Delifer, Pierre Tiberghien, Chaturaka Rodrigo, Francesca Trespidi, Micol Angelini, Giada Rossini, Tiziana Lazzarotto, Francesca Conti, Irene Cassaniti, Fausto Baldanti, Francesca Rovida, Alessandro Ferrari, Davide Mileto, Alessandro Mancon, Laurent Abel, Anne Puel, Aurélie Cobat, Charles M Rice, Dániel Cadar, Jonas Schmidt-Chanasit, Johannes F Scheid, Jacob E Lemieux, Eric S Rosenberg, Marianna Agudelo, Stuart G Tangye, Alessandro Borghesi, Guillaume André Durand, Emilie Duburcq-Gury, Braulio M Valencia, Andrew R Lloyd, Anna Nagy, Margaret M MacDonald, Yannick Simonin, Shen-Ying Zhang, Jean-Laurent Casanova

{"title":"Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.","authors":"Adrian Gervais, Paul Bastard, Lucy Bizien, Céline Delifer, Pierre Tiberghien, Chaturaka Rodrigo, Francesca Trespidi, Micol Angelini, Giada Rossini, Tiziana Lazzarotto, Francesca Conti, Irene Cassaniti, Fausto Baldanti, Francesca Rovida, Alessandro Ferrari, Davide Mileto, Alessandro Mancon, Laurent Abel, Anne Puel, Aurélie Cobat, Charles M Rice, Dániel Cadar, Jonas Schmidt-Chanasit, Johannes F Scheid, Jacob E Lemieux, Eric S Rosenberg, Marianna Agudelo, Stuart G Tangye, Alessandro Borghesi, Guillaume André Durand, Emilie Duburcq-Gury, Braulio M Valencia, Andrew R Lloyd, Anna Nagy, Margaret M MacDonald, Yannick Simonin, Shen-Ying Zhang, Jean-Laurent Casanova","doi":"10.1084/jem.20240942","DOIUrl":"10.1084/jem.20240942","url":null,"abstract":"Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections. Auto-Abs neutralizing high concentrations of IFN-α2, IFN-β, and/or IFN-ω are present in the single case of severe Powassan virus (POWV) encephalitis studied, two of three cases of severe Usutu virus (USUV) infection studied, and the most severe of 24 cases of Ross River virus (RRV) disease studied. These auto-Abs are not found in any of the 137 individuals with silent or mild infections with these three viruses. Thus, auto-Abs neutralizing type I IFNs underlie an increasing list of severe arboviral diseases due to Flaviviridae (WNV, TBEV, POWV, USUV) or Togaviridae (RRV) viruses transmitted to humans by mosquitos (WNV, USUV, RRV) or ticks (TBEV, POWV).","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558021","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}

引用次数: 0

Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer. 髓系激活可清除腹水，并揭示转移性卵巢癌的消退依赖于 IL27。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-21 DOI: 10.1084/jem.20231967

Brennah Murphy, Taito Miyamoto, Bryan S Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P Zhu, Daniel T Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang

{"title":"Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer.","authors":"Brennah Murphy, Taito Miyamoto, Bryan S Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P Zhu, Daniel T Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang","doi":"10.1084/jem.20231967","DOIUrl":"10.1084/jem.20231967","url":null,"abstract":"Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681722","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}

引用次数: 0