Article
Urology & Nephrology
Georg R. Herrnstadt, Christoph B. Niehus, Torben Ramcke, Julia Hagenstein, Laura-Isabell Ehnold, Anna Nosko, Matthias T. Warkotsch, Frederic C. Feindt, Simon Melderis, Hans-Joachim Paust, Varshi Sivayoganathan, Saskia-Larissa Jauch-Speer, Milagros N. Wong, Daniela Indenbirken, Christian F. Krebs, Tobias B. Huber, Ulf Panzer, Victor G. Puelles, Malte A. Kluger, Oliver M. Steinmetz
Summary: Previous studies have identified a unique Treg population, known as RORyt+ Tregs, which possess enhanced immunosuppressive capacity and therapeutic potential. However, they are also capable of secreting pro-inflammatory IL-17A. This study investigated the absence of RORyt+ Tregs in glomerulonephritis (GN) and found that their absence significantly aggravated kidney injury, demonstrating their overall kidney-protective properties. Analyses showed that RORyt+ Tregs were broadly immunosuppressive, and their absence had a negative impact on GN.
KIDNEY INTERNATIONAL
(2023)
Article
Oncology
Hiroshi Kano, Kouji Izumi, Kaoru Hiratsuka, Ren Toriumi, Ryunosuke Nakagawa, Shuhei Aoyama, Taiki Kamijima, Takafumi Shimada, Renato Naito, Suguru Kadomoto, Hiroaki Iwamoto, Hiroshi Yaegashi, Shohei Kawaguchi, Takahiro Nohara, Kazuyoshi Shigehara, Yoshifumi Kadono, Yohei Saito, Kyoko Nakagawa-Goto, Kazuaki Yoshioka, Hiroki Nakata, Wen-Jye Lin, Atsushi Mizokami
Summary: This study identified a regulation of the androgen receptor (AR)-controlled pathway that promotes migration potential in prostate cancer cells. The increase in migration potential was associated with upregulated CCL20 expression and enhanced AKT phosphorylation and Snail expression.
Article
Biochemistry & Molecular Biology
Tao Xie, Du-Jiang Fu, Zhi-Min Li, Dao-Jun Lv, Xian-Lu Song, Yu-Zhong Yu, Chong Wang, Kang-Jin Li, Baoqian Zhai, Jiacheng Wu, Ning-Han Feng, Shan-Chao Zhao
Summary: This study reveals that circSMARCC1 upregulates the secretion of chemokine CCL20 by sponging miR-1322, which mediates the interaction between tumor cells and TAMs, promoting the progression of PCa.
Article
Immunology
Chenchen Ye, Xinxue Guo, Jiani Wu, Minhua Wang, Haiyan Ding, Xianzhi Ren
Summary: Activation and polarization of macrophages mediated by CCL20/CCR6 may promote adenoid epithelial inflammation in adenoid hypertrophy. The CCL20/CCR6 axis could be a critical therapeutic target for treatment.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Endocrinology & Metabolism
Denghai Wu, Binhua Jiang, Jianan Lian, Jian Liu
Summary: The study aimed to investigate the expression and biological functions of SPARCL1 in the tumor microenvironment of colorectal cancer liver metastases (CRCLM) and provide a new molecular marker for targeted therapy. The results showed that upregulation of SPARCL1 could reduce the metastatic foci number, collagen deposition, and liver fibrosis, and play an important role in immune responses and epithelial-to-mesenchymal transition (EMT).
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Biochemistry & Molecular Biology
David Schumacher, Elisa A. Liehn, Anjana Singh, Adelina Curaj, Erwin Wijnands, Sergio A. Lira, Frank Tacke, Joachim Jankowski, Erik A. L. Biessen, Emiel P. C. van der Vorst
Summary: The study found that CCR6 plays an important role in ischemia-reperfusion injury after acute myocardial infarction, exerting protective effects on the heart through bone marrow cells. Increasing CCR6-dependent immune mechanisms may represent an interesting therapeutic target for cardiac damage and inflammation.
Article
Multidisciplinary Sciences
Kamila Baran, Jacek Kordiak, Slawomir Jablonski, Ewa Brzezianska-Lasota
Summary: This study evaluated the expression levels of CCR6/CCL20 mRNA and non-coding RNAs (ncRNAs) such as miR-150 and linc00673 in NSCLC tissue. It was found that CCL20 mRNA was upregulated while CCR6 mRNA was downregulated in tumor tissue. In addition, the expression levels of miR-150 and linc00673 in serum extracellular vesicles showed associations with tumor staging and histopathological type.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Michelle Fennen, Toni Weinhage, Vanessa Kracke, Johanna Intemann, Georg Varga, Corinna Wehmeyer, Dirk Foell, Adelheid Korb-Pap, Thomas Pap, Berno Dankbar
Summary: The study demonstrated the involvement of myostatin in regulating joint inflammation by recruiting Th17 cells to inflammatory sites. Blockade of the CCL20-CCR6 axis by inhibiting myostatin could be a promising treatment option for chronic inflammatory diseases such as arthritis.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Teizo Yoshimura, Chunning Li, Yuze Wang, Akihiro Matsukawa
Summary: Breast cancer is a common cancer worldwide, and metastasis is the main cause of cancer-related death. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was identified as a chemotactic factor for monocytes, and its role in cancer development and progression was investigated. Studies showed positive correlations between MCP-1 production in tumors and TAM infiltration, as well as cancer progression. MCP-1 was found to promote breast cancer metastasis to the lung and brain, but not bone. The mechanisms of MCP-1 production in the breast cancer microenvironment were also reported.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Holger Loerchner, Laia Canes Esteve, Maria Elisa Goes, Roxanne Harzenetter, Nathalie Brachmann, Praveen Gajawada, Stefan Guenther, Nicolas Doll, Jochen Poeling, Thomas Braun
Summary: This study reveals that TNF alpha recruits VEGFA-expressing neutrophils for muscle tissue revascularization through the CCL20-CCR6 axis. This finding provides a promising approach for revascularization, especially in diabetic conditions.
CIRCULATION RESEARCH
(2023)
Article
Gastroenterology & Hepatology
David N. Hanna, Paula Marincola Smith, Sergey V. Novitskiy, M. Kay Washington, Jinghuan Zi, Connie J. Weaver, Jalal A. Hamaamen, Keeli B. Lewis, Jing Zhu, Jing Yang, Qi Liu, R. Daniel Beauchamp, Anna L. Means
Summary: Loss of SMAD4 in colonic epithelial cells can increase CCL20 expression and recruitment of CCR6+ immune cells, leading to a greater susceptibility to colon cancer.
Review
Immunology
Heikrujam Thoihen Meitei, Nandadeep Jadhav, Girdhari Lal
Summary: CCR6 and CCL20 play crucial roles in cell migration and inflammatory conditions, with strong associations found between their expression and disease severity in various autoimmune disorders. Targeting the CCR6-CCL20 axis shows promise in controlling autoimmune diseases by preventing immune cell migration and reducing inflammation.
AUTOIMMUNITY REVIEWS
(2021)
Article
Dermatology
L. Wang, M. Yang, X. Wang, B. Cheng, Q. Ju, D. Z. Eichenfield, B. K. Sun
Summary: The study showed that glucocorticoids can increase CCL20 expression in human keratinocytes and murine skin by directly binding to the enhancer region of CCL20. This mechanism may contribute to the inflammation observed in steroid-exacerbated skin conditions.
BRITISH JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Maria Braoudaki, Mohammed Saqif Ahmad, Denis Mustafov, Sara Seriah, Mohammad Naseem Siddiqui, Shoib Sarwar Siddiqui
Summary: Colorectal cancer is a common and deadly disease, and early diagnosis is crucial for patient prognosis. However, little progress has been made in identifying biomarkers for early diagnosis, resulting in high mortality rates in advanced stages. This review investigates the role of chemokines and chemokine receptors in colorectal cancer, discusses their potential as personalized therapeutic approaches, and summarizes the progress in drug resistance research.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Mingxuan Zhu, Liangliang Bai, Xiaoxia Liu, Shaoyong Peng, Yumo Xie, Hong Bai, Huichuan Yu, Xiaolin Wang, Ping Yuan, Rui Ma, Jinxin Lin, Linping Wu, Meijin Huang, Yingjie Li, Yanxin Luo
Summary: This study revealed that CSF1R is a novel identified dependence receptor silenced in colorectal cancer (CRC). The silence abalienates its ligands to stimulate CSF1R expressed on M2 TAMs, which is an appealing therapeutic target for M2 TAM depletion and CRC treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Yan Song, Ting Du, Arghya Ray, Krishan Chauhan, Mehmet Samur, Nikhil Munshi, Dharminder Chauhan, Kenneth C. Anderson
BLOOD CANCER JOURNAL
(2021)
Review
Gastroenterology & Hepatology
Markus H. Frank, Brian J. Wilson, Jason S. Gold, Natasha Y. Frank
Summary: The concept of cancer stem cells (CSCs) suggests a hierarchy within tumors where a minority of more primitive cells give rise to more differentiated cells that make up the tumor bulk, but are not capable of perpetuating tumors on their own. CSCs may drive therapeutic resistance and cancer progression, and their identification and isolation methods have been established. Single-cell omics technologies offer opportunities to discover novel molecular pathways for CRC eradication.
Article
Multidisciplinary Sciences
Mehmet Kemal Samur, Mariateresa Fulciniti, Anil Aktas Samur, Abdul Hamid Bazarbachi, Yu-Tzu Tai, Rao Prabhala, Alejandro Alonso, Adam S. Sperling, Timothy Campbell, Fabio Petrocca, Kristen Hege, Shari Kaiser, Herve Avet Loiseau, Kenneth C. Anderson, Nikhil C. Munshi
Summary: Relapse following BCMA targeted CAR T-cell therapy in multiple myeloma patients is often due to biallelic loss of BCMA, which hinders the proliferation of CAR T cells and results in lack of response to retreatment. Single cell genomic characterization is essential for detecting BCMA gene alterations to improve treatment outcomes.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Tomasz Sewastianik, Juerg R. Straubhaar, Jian-Jun Zhao, Mehmet K. Samur, Keith Adler, Helen E. Tanton, Vignesh Shanmugam, Omar Nadeem, Peter S. Dennis, Vinodh Pillai, Jianli Wang, Meng Jiang, Jianhong Lin, Ying Huang, Daniel Brooks, Mary Bouxsein, David M. Dorfman, Geraldine S. Pinkus, Davide F. Robbiani, Irene M. Ghobrial, Bogdan Budnik, Petr Jarolim, Nikhil C. Munshi, Kenneth C. Anderson, Ruben D. Carrasco
Summary: The deletion of miR-15a/16-1 cluster in murine GC B cells induces moderate but widespread molecular and functional changes, leading to the development of mature B-cell neoplasms resembling human extramedullary plasmacytoma and lymphoma. The low expression levels of miR-15a/16 in human primary EP, primarily associated with del(13q) loss, highlights the tumor-suppressor role of this cluster in plasma cell and B-cell malignancies.
Editorial Material
Oncology
Jonathan Pastrana Del Valle, Jason S. Gold
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Jonathan Pastrana Del Valle, Nathanael R. Fillmore, George Molina, Mark Fairweather, Jiping Wang, Thomas E. Clancy, Stanley W. Ashley, Richard D. Urman, Edward E. Whang, Jason S. Gold
Summary: In the VHA system, factors such as race, marital status, and employment status are associated with pancreatic cancer resection, while geographic region and employment status are associated with survival after resection. However, factors like race, Hispanic ethnicity, marital status, and Social Deprivation Index are not independently associated with survival after resection. Further studies are needed to explore the basis for these inequities.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Hematology
Debora Soncini, Claudia Martinuzzi, Pamela Becherini, Elisa Gelli, Samantha Ruberti, Katia Todoerti, Luca Mastracci, Paola Contini, Antonia Cagnetta, Antonella Laudisi, Fabio Guolo, Paola Minetto, Maurizio Miglino, Sara Aquino, Riccardo Varaldo, Daniele Reverberi, Matteo Formica, Mario Passalacqua, Alessio Nencioni, Antonino Neri, Mehmet K. Samur, Nikhil C. Munshi, Mariateresa Fulciniti, Roberto M. Lemoli, Michele Cea
Summary: Recent studies have found aberrant splicing in cancer cells and suggested it as a potential therapeutic strategy. This study evaluated the expression of spliceosome machinery components in multiple myeloma cells and found that modulating splicing can impair cell growth and survival. The findings suggest that targeting splicing could make multiple myeloma patients more vulnerable to BCL2 inhibitors.
Article
Hematology
Nicola Giesen, Nagarajan Paramasivam, Umut H. Toprak, Daniel Huebschmann, Jing Xu, Sebastian Uhrig, Mehmet Samur, Stella Baehr, Martina Froehlich, Sadaf S. Mughal, Elias K. Mai, Anna Jauch, Carsten Muller-Tidow, Benedikt Brors, Nikhil Munshi, Hartmut Goldschmidt, Niels Weinhold, Matthias Schlesner, Marc S. Raab
Summary: This study provides comprehensive genomic characterization of heavily pretreated relapsed/refractory multiple myeloma patients, revealing a complex mutational landscape and potential therapeutic targets. The findings highlight the impact of specific gene mutations on patient survival and suggest potential therapeutic implications.
Article
Oncology
Jonathan Pastrana Del Valle, David A. Mahvi, Mark Fairweather, Jiping Wang, Thomas E. Clancy, Stanley W. Ashley, Richard D. Urman, Edward E. Whang, Jason S. Gold
Summary: Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.
JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Maximilian Merz, Almuth Maria Anni Merz, Jie Wang, Lei Wei, Qiang Hu, Nicholas Hutson, Cherie Rondeau, Kimberly Celotto, Ahmed Belal, Ronald Alberico, AnneMarie W. Block, Hemn Mohammadpour, Paul K. Wallace, Joseph Tario, Jesse Luce, Sean T. Glenn, Prashant Singh, Megan M. Herr, Theresa Hahn, Mehmet Samur, Nikhil Munshi, Song Liu, Philip L. McCarthy, Jens Hillengass
Summary: This study characterizes osteolytic lesions (OL) in multiple myeloma patients using single-cell RNA sequencing (scRNA-seq), revealing specifically regulated genes in OL compared to random bone marrow samples, as well as their response to induction therapy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ram Ajore, Abhishek Niroula, Maroulio Pertesi, Caterina Cafaro, Malte Thodberg, Molly Went, Erik L. Bao, Laura Duran-Lozano, Aitzkoa Lopez de Lapuente Portilla, Thorunn Olafsdottir, Nerea Ugidos-Damboriena, Olafur Magnusson, Mehmet Samur, Caleb A. Lareau, Gisli H. Halldorsson, Gudmar Thorleifsson, Gudmundur L. Norddahl, Kristbjorg Gunnarsdottir, Asta Foersti, Hartmut Goldschmidt, Kari Hemminki, Frits van Rhee, Scott Kimber, Adam S. Sperling, Martin Kaiser, Kenneth Anderson, Ingileif Jonsdottir, Nikhil Munshi, Thorunn Rafnar, Anders Waage, Niels Weinhold, Unnur Thorsteinsdottir, Vijay G. Sankaran, Kari Stefansson, Richard Houlston, Bjorn Nilsson
Summary: This integrative study investigates over a thousand variants associated with multiple myeloma, identifying potential causal variants at six risk loci and highlighting the role of gene-regulatory changes in plasma cells and B-cells in mediating disease susceptibility.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Romain Lannes, Mehmet Samur, Aurore Perrot, Celine Mazzotti, Marion Divoux, Titouan Cazaubiel, Xavier Leleu, Anais Schavgoulidze, Marie-Lorraine Chretien, Salomon Manier, Didier Adiko, Frederique Orsini-Piocelle, Francois Lifermann, Sabine Brechignac, Lauris Gastaud, Didier Bouscary, Margaret Macro, Alice Cleynen, Mohamad Mohty, Nikhil Munshi, Jill Corre, Herve Avet-Loiseau
Summary: Using single-cell genomics, it was found that high-risk events in multiple myeloma (MM) patients are often missed at diagnosis and only selected at relapse. This suggests the need for more aggressive treatment at diagnosis to prevent these aggressive cells from becoming dominant clones.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Keiji Kurata, Anna-James Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
Summary: Multiple myeloma (MM) is a plasma cell malignancy associated with aberrant immunoglobulin production and proteotoxic stress. In this study, we identified glutamyl-prolyl-tRNA synthetase (GluProRS) as a potential therapeutic target. By developing a novel inhibitor called NCP26, we demonstrated its significant anti-tumour activity in various in vitro and in vivo systems, overcoming metabolic adaptation observed with other inhibitors. Our findings suggest a complex pro-apoptotic response beyond the integrated stress response, involving downregulated proline-rich motif-containing proteins as downstream effectors and establishing a novel determinant in MM pathobiology.
BLOOD CANCER JOURNAL
(2023)
Correction
Oncology
Keiji Kurata, Anna James-Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
BLOOD CANCER JOURNAL
(2023)
Article
Multidisciplinary Sciences
Ram Ajore, Abhishek Niroula, Maroulio Pertesi, Caterina Cafaro, Malte Thodberg, Molly Went, Erik L. Bao, Laura Duran-Lozano, Aitzkoa Lopez de Lapuente Portilla, Thorunn Olafsdottir, Nerea Ugidos-Damboriena, Olafur Magnusson, Mehmet Samur, Caleb A. Lareau, Gisli H. Halldorsson, Gudmar Thorleifsson, Gudmundur L. Norddahl, Kristbjorg Gunnarsdottir, Asta Forsti, Hartmut Goldschmidt, Kari Hemminki, Frits van Rhee, Scott Kimber, Adam S. Sperling, Martin Kaiser, Kenneth Anderson, Ingileif Jonsdottir, Nikhil Munshi, Thorunn Rafnar, Anders Waage, Niels Weinhold, Unnur Thorsteinsdottir, Vijay G. Sankaran, Kari Stefansson, Richard Houlston, Bjorn Nilsson
Summary: In this study, non-coding variants associated with multiple myeloma (MM) were investigated using a combination of methods. The results showed that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identified potential causal variants at six risk loci. Three of these variants were found to have causal activity at specific genomic positions in an endogenous chromosomal context in vivo. This study provides a systematic functional analysis of risk loci for a hematologic malignancy.
NATURE COMMUNICATIONS
(2022)