Review
Immunology
Sophie Liot, Jonathan Balas, Alexandre Aubert, Laura Prigent, Perrine Mercier-Gouy, Bernard Verrier, Philippe Bertolino, Ana Hennino, Ulrich Valcourt, Elise Lambert
Summary: Pancreatic cancer, especially PDAC, has a poor prognosis with low survival rates, mainly due to its dense stroma deposition and immune suppression in the TME. Research on TME composition may lead to new therapeutic targets for better treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Maria Joao Amaral, Mariana Amaral, Joao Freitas, Rui Caetano Oliveira, Marco Serodio, Maria Augusta Cipriano, Jose Guilherme Tralhao
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, which accounts for 80% of its volume. The amount of stroma may affect prognosis, but its specific impact remains uncertain. This study aimed to investigate prognostic factors for PDAC patients undergoing surgery, including the impact of tumor stroma area (TSA). A retrospective study was conducted with PDAC patients who underwent surgical resection. TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa were identified as independent risk factors for mortality in PDAC patients undergoing surgery. Regarding TSA, a larger TSA seemed to be associated with longer overall survival (OS) for all stages. In stage II patients, a larger TSA was significantly associated with R0 resection, while in stage III patients, a larger TSA was significantly associated with a lower histological grade, higher preoperative AP levels, and lower preoperative AST levels. Patients with PDAC undergoing surgical resection and having preoperative CA19.9 > 500 U/L and AST >= 100 U/L had a higher risk of recurrence, although tumor stroma may have a protective effect in these patients.
Review
Oncology
Yang Wu, Chun Zhang, Kuirong Jiang, Jens Werner, Alexandr V. Bazhin, Jan G. D'Haese
Summary: PDAC progression is influenced by PSCs, which through interactions with PCCs and other stroma cells, establish a tumor microenvironment that promotes tumor growth, metastasis, and chemoresistance. Targeting stroma has emerged as a promising strategy for PDAC therapy, with several novel strategies proposed to intervene in this complex crosstalk.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Jiahong Jiang, Yaping Xu, Lianpeng Chang, Guoqing Ru, Xuefeng Xia, Ling Yang, Xin Yi, Zheling Chen, Dong-Sheng Huang, Liu Yang
Summary: This study revealed the presence of driver gene mutations in PDAC stroma, indicating that the genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and may help guide a more precise treatment paradigm in therapeutic options.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Yanmiao Huo, Jian Yang, Jiahao Zheng, Dapeng Xu, Minwei Yang, Lingye Tao, Hongfei Yao, Xueliang Fu, Jianyu Yang, Dejun Liu, Rong Hua, Junfeng Zhang, Yongwei Sun, Lipeng Hu, Wei Liu
Summary: This study found that SPON1 is significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) and promotes tumor growth and development by activating the sIL-6R/gp130/STAT3 pathway. These results suggest that SPON1 may be a potential therapy target for PDAC patients.
CELL PROLIFERATION
(2022)
Article
Biology
Jil-Madeline Homeier, Katrin Bundkirchen, Marcel Winkelmann, Tilman Graulich, Borna Relja, Claudia Neunaber, Christian Macke
Summary: This study investigated the use of a selective IL-6 trans-signaling inhibition in multiple trauma patients to prevent MODS. The results showed that the IL-6 trans-signaling inhibitor sgp130Fc had little effect on cytokine levels, indicating limited effectiveness in preventing the development of MODS.
Article
Oncology
Tomohiko Shinkawa, Kenoki Ohuchida, Yuki Mochida, Kukiko Sakihama, Chika Iwamoto, Toshiya Abe, Noboru Ideno, Yusuke Mizuuchi, Koji Shindo, Naoki Ikenaga, Taiki Moriyama, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Summary: The presence of abundant stroma in pancreatic ductal adenocarcinoma (PDAC) can define the PDAC phenotype and induce distinct therapeutic responses. Cancer-associated fibroblasts (CAFs) maintain the differentiated PDAC phenotype through secreting niche factors and induce different drug responses.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Stefan Schreiber, Konrad Aden, Joana P. Bernardes, Claudio Conrad, Florian Tran, Hanna Hoeper, Valery Volk, Neha Mishra, Johanna Ira Blase, Susanna Nikolaus, Johannes Bethge, Tanja Kuehbacher, Christoph Roecken, Minhu Chen, Ian Cottingham, Niclas Petri, Birgitte B. Rasmussen, Juliane Lokau, Lennart Lenk, Christoph Garbers, Friedrich Feuerhake, Stefan Rose-John, Georg H. Waetzig, Philip Rosenstiel
Summary: The study on the treatment of IBD patients with the trans-signaling inhibitor olamkicept (sgp130Fc) showed that patients tolerated the treatment well, with 44% showing clinical response and 19% achieving clinical remission. The clinical effectiveness was associated with target inhibition and marked transcriptional changes in the inflamed mucosa.
Review
Oncology
Nicole Lintern, Andrew M. Smith, David G. Jayne, Yazan S. Khaled
Summary: Pancreatic cancer is highly lethal with low survival rate. The resistance to current therapies is largely attributed to the dense tissue surrounding the cancer cells. Photodynamic therapy (PDT) has shown potential in killing pancreatic cancer cells and altering the surrounding tissue.
Article
Biochemistry & Molecular Biology
Rebekah Robinson, Daria Brown, Lara Churchwell, Tae-Jin Lee, Sai Karthik Kodeboyina, Justin Bloom, Ashok Sharma, Shruti Sharma
Summary: The study revealed significant gene expression changes in HRECs caused by IL-6 trans-signaling activation. Several novel genes associated with IL-6 signaling or endothelial dysfunction were identified. Inhibition of IL-6 trans-signaling reversed these changes, highlighting the therapeutic potential of this approach.
Article
Oncology
Qiangda Chen, Hanlin Yin, Siyao Liu, Sami Shoucair, Ni Ding, Yuan Ji, Jicheng Zhang, Dansong Wang, Tiantao Kuang, Xuefeng Xu, Jun Yu, Wenchuan Wu, Ning Pu, Wenhui Lou
Summary: Tumor-associated N2 neutrophils were found to significantly increase, while a low N1/N2 ratio was associated with poorly differentiated tumors, easier lymph node metastases, and higher TNM stage. A high N1/N2 ratio was identified as a significant prognostic indicator for overall survival and recurrence-free survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Yuqing Zhang, Morgan Coleman, Rolf A. Brekken
Summary: Hypoxia is a common feature of solid tumors that promotes tumor progression and metastasis. Hypoxia, mainly mediated by the HIF family, leads to tumor cell migration, proliferation, metabolic changes, and therapy resistance. Additionally, hypoxia affects various cellular and non-cellular compartments in the tumor stroma, including disordered tumor vasculature and ECM homeostasis. Hypoxia also has complex and sometimes contradictory effects on immune cell function, contributing to an immunosuppressive environment.
Review
Biochemistry & Molecular Biology
Valentina Giansante, Gianmarco Stati, Silvia Sancilio, Emanuela Guerra, Saverio Alberti, Roberta Di Pietro, Joerg D. Hoheisel
Summary: Pancreatic cancer is the seventh leading cause of cancer-related death, and its incidence is increasing each year. The low relative survival rate and challenges of heterogeneity and tumor microenvironment in pancreatic cancer have emphasized the need for novel therapeutic strategies. This review focuses on the role of necroptosis in pancreatic cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Weijian Kong, Zhengsheng Liu, Mengnan Sun, Huiqin Liu, Chao Kong, Jie Ma, Rui Wang, Feng Qian
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fibrotic tumor with abundant activated pancreatic stellate cells (PSCs). Inhibiting autophagy and activating vitamin D receptor (VDR) signaling can improve the response of PDAC to immunotherapy. We developed a PSC deactivator that can both activate VDR signaling and inhibit autophagy, and showed that it significantly enhanced the response of PDAC to immunotherapy and chemotherapy.
Article
Oncology
Xuan Zou, Xuan Lin, He Cheng, Yusheng Chen, Ruijie Wang, Mingjian Ma, Yu Liu, Zhengjie Dai, Yesboli Tasiheng, Yu Yan, Qinqin Hou, Fei Ding, Huan Chen, Xianjun Yu, Xu Wang, Chen Liu
Summary: This study systematically revealed the cellular properties and prognostic values of intratumoral TLSs in pancreatic ductal adenocarcinoma (PDAC) and described the potential impact of neoadjuvant treatment (NAT) on TLS development and function.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Stefan Rose-John
Summary: Interleukin-6 is an inflammatory cytokine whose level is elevated in inflammatory states, triggering cell-specific responses. The activation of gp130 in hepatocytes produces both liver-specific and systemic effects.
Article
Cell Biology
Michael Dudek, Kerstin Lohr, Sainitin Donakonda, Tobias Baumann, Max Lu, Silke Hegenbarth, Lena Duebbel, Carola Eberhagen, Savvoula Michailidou, Abdallah Yassin, Marco Prinz, Bastian Popper, Stefan Rose-John, Hans Zischka, Percy A. Knolle
Summary: This study reveals distinct immunometabolic features of liver sinusoidal endothelial cells (LSECs) and LSEC-primed CD8 T cells compared with immunogenic dendritic cells and effector CD8 T cells, highlighting the local metabolism and function of T cells in the liver.
Article
Cell Biology
Alice Prieto Huarcaya, Susy Drobny, Andre R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert, Denise Balta, Christian Werner, Tania Rizo, Lisa Gallwitz, Simon Bub, Iva Stojkovska, Nandkishore R. Belur, Jens Fogh, Joseph R. Mazzulli, Wei Xiang, Amitkumar Fulzele, Mario Dejung, Markus Sauer, Beate Winner, Stefan Rose-John, Philipp Arnold, Paul Saftig, Friederike Zunke
Summary: This study suggests that enhancing SNCA degradation through the application of rHsCTSD can reduce SNCA aggregates in the brains of PD patients and restore endo-lysosome and autophagy function.
Editorial Material
Biochemistry & Molecular Biology
Andreas Herrlich, Eirini Kefaloyianni, Stefan Rose-John
Article
Biochemistry & Molecular Biology
Sophia Kirschke, Ireti Ogunsulire, Balachandar Selvakumar, Neele Schumacher, Tanya Sezin, Stefan Rose-John, Alexander Scheffold, Christoph Garbers, Juliane Lokau
Summary: The cytokine IL-2 plays a crucial role in immune homeostasis. This study demonstrates that metalloproteases ADAM10 and ADAM17 can cleave the IL-2R alpha, generating a soluble ectodomain that inhibits IL-2 signaling in T cells. Manipulating the cleavage of IL-2R alpha offers a potential opportunity to alter IL-2 function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Torben Mentrup, Anna Yamina Stumpff-Niggemann, Nadja Leinung, Christine Schlosser, Katja Schubert, Rebekka Wehner, Antje Tunger, Valentin Schatz, Patrick Neubert, Ann-Christine Gradtke, Janina Wolf, Stefan Rose-John, Paul Saftig, Alexander Dalpke, Jonathan Jantsch, Marc Schmitz, Regina Fluhrer, Ilse D. Jacobsen, Bernd Schroeder
Summary: Dectin-1 plays a critical role in recognizing fungal pathogens through pattern recognition receptors on immune cells. Activation of Dectin-1a results in the formation of a stable receptor fragment lacking the ligand binding domain, which contributes to signal transduction in phagosomal membranes and is terminated by intramembrane proteases SPPL2a and 2b.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Maria Angeles Rodriguez-Hernandez, David Carneros, Maria Nunez-Nunez, Ramon Coca, Rosario Baena, Gema M. Lopez-Ruiz, Maria Elena Cano-Serrano, Alberto Martinez-Telleria, Ana Fuentes-Lopez, Juan Manuel Praena-Fernandez, Christoph Garbers, Jose Hernandez-Quero, Federico Garcia, Stefan Rose-John, Matilde Bustos
Summary: IL-6 signaling variables serve as useful tools for early identification and stratification of COVID-19 patients, with significant implications for treatment and clinical decision-making.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Tor Henrik Anderson Tvedt, Stefan Rose-John, Galina Tsykunova, Aymen Bushra Ahmed, Tobias Gedde-Dahl, Elisabeth Ersvaer, Oystein Bruserud
Summary: Graft-versus-host disease (GVHD) is a common complication after stem cell transplantation and is mediated by T cells. IL-6 plays a role in both pro-inflammatory and anti-inflammatory effects, and it modulates T cell response. The study found that CD3(+)CD4(+) and CD3(+)C8(+) T cells have different responses to IL-6 signaling, and these responses are influenced by antithymocyte globulin treatment. These findings suggest that IL-6 targeting after transplantation may have varied effects on patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Aikaterini Gatsiou, Simon Tual-Chalot, Matteo Napoli, Almudena Ortega-Gomez, Tommy Regen, Rachit Badolia, Valeriana Cesarini, Claudia Garcia-Gonzalez, Raphael Chevre, Giorgia Ciliberti, Carlos Silvestre-Roig, Maurizio Martini, Jedrzej Hoffmann, Rana Hamouche, Joseph R. Visker, Nikolaos Diakos, Astrid Wietelmann, Domenico Alessandro Silvestris, Georgio Georgiopoulos, Ali Moshfegh, Andre Schneider, Wei Chan, Stefan Guenther, Johanne Backs, Shin Kwak, Craig H. Selzman, Kimon Stamatelopoulos, Stefan Rose-John, Christian Trautwein, Ioakim Spyridopoulos, Thomas Braun, Ari Waisman, Angela Gallo, Stavros G. Drakos, Stefanie Dimmeler, Markus Sperandio, Oliver Soehnlein, Konstantinos Stellos
Summary: RNA editor ADAR2 regulates endothelial responses to IL-6, controlling leukocyte trafficking in inflamed and ischemic tissues. ADAR2 is required for IL-6 trans-signaling and immune cell infiltration through suppressing primary microRNA processing.
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Immunology
Agatha Schwarz, Rebecca Philippsen, Serena G. Piticchio, Jan N. Hartmann, Robert Haesler, Stefan Rose-John, Thomas Schwarz
Summary: The organ-specific microbiome, particularly the skin microbiome, plays a crucial role in tissue homeostasis by regulating the inflammatory response. Short chain fatty acids (SCFA) induce regulatory T cells (Treg) in the skin and their signal is mediated by the receptor HCA2. Knock-out of HCA2 results in stronger inflammation and a switch of Treg from a suppressive to a proinflammatory type, indicating that the skin microbiome dictates the outcome of the inflammatory reaction.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Stefan Rose-John, Brendan J. Jenkins, Christoph Garbers, Jens M. Moll, Juergen Scheller
Summary: This review discusses the discovery of the IL-6 trans-signalling pathway and the development of biologics that specifically inhibit this pathway. Targeting IL-6 trans-signalling can decrease disease-promoting activities of IL-6 without blocking its protective actions.
NATURE REVIEWS IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
P. Bradtke, J. Roesch, D. Reimers, K. Yan, S. Rose-John, H. -W. Mittruecker
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
E. V. M. Huth, L. C. Heinig, K. Yan, P. Bradtke, N. Lory, T. Wiech, S. Rose-John, H. -W. Mittruecker
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Oncology
Melanie Spitzner, Kristin Koerdel, Thomas Meyer, Niklas Engels, Florian Krause, Jochen Gaedcke, Lena-Christin Conradi, Martin Haubrock, Tim Beissbarth, Andreas Leha, Steven A. Johnsen, B. Michael Ghadimi, Stefan Rose-John, Jurgen Wienands, Marian Grade
ONCOLOGY RESEARCH AND TREATMENT
(2022)
