Article
Biochemistry & Molecular Biology
Tatsuya Kometani, Koki Kamo, Taketomo Kido, Nobuyoshi Hiraoka, Taku Chibazakura, Kenji Unno, Keisuke Sekine
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a serious and chemotherapy-resistant disease. We established a co-culture system using PDAC patient-derived cancer cells and stellate cells from human induced pluripotent stem cells to mimic the tumor microenvironment (TME) of PDAC. This system successfully demonstrated the interaction between cancer cells and stellate cells and replicated some features of PDAC in vitro. Furthermore, the co-culture system showed potential for drug treatment testing in vitro.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Julie Auwercx, Philippe Kischel, Thibaut Lefebvre, Nicolas Jonckheere, Alison Vanlaeys, Stephanie Guenin, Silviya Radoslavova, Isabelle Van Seuningen, Halima Ouadid-Ahidouch, Hemant M. Kocher, Isabelle Dhennin-Duthille, Mathieu Gautier
Summary: Pancreatic diseases are characterized by activated pancreatic stellate cells (PSCs), which play important roles in tumor stroma. TRPM7 channels have been found to regulate the activation and proliferation of PSCs, and the expression of TRPM7 is associated with the activation status of PSCs.
Article
Medicine, General & Internal
Xiuhui Shi, Min Wang, Yuqing Zhang, Xingjun Guo, Mingyang Liu, Zhijun Zhou, Yan Zhao, Ruizhi He, Yang Gao, Yuhui Liu, Shutao Pan, Min Zhou, Chunle Zhao, Taoyuan Yin, Xu Li, Hebin Wang, Jingxuan Yang, Feng Zhu, Min Li, Renyi Qin
Summary: High expression levels of alpha-SMA and hypoxia markers are associated with poor prognosis in pancreatic cancer patients. Mechanistically, hypoxia induces HGF expression and secretion in PSC via HIF-1 alpha, which then activates Met and suppresses pancreatic cancer cell sensitivity to EGFR inhibitors. The combination of EGFR inhibitor and Met inhibitor shows promise for pancreatic cancer treatment based on the demonstrated signaling axis between PSC and cancer cells.
Article
Immunology
Jessica M. Sierra, Florencia Secchiari, Sol Y. Nunez, Ximena L. Raffo Iraolagoitia, Andrea Ziblat, Adrian D. Friedrich, Maria V. Regge, M. Cecilia Santilli, Nicolas I. Torres, Mariana Gantov, Aldana Trotta, Carlos Ameri, Gonzalo Vitagliano, Hernando Rios Pita, Luis Rico, Agustin Rovegno, Nicolas Richards, Carolina I. Domaica, Norberto W. Zwirner, Mercedes B. Fuertes
Summary: NK cells in clear cell renal cell carcinoma patients display altered phenotype and impaired effector functions, with a high frequency of tumor-infiltrating PD-L1(+) NK cells suggesting immunoregulatory functions. In vitro studies show that PD-L1(hi) NK cells exhibit an activated phenotype and enhanced effector functions, while also inhibiting CD8(+) T cell proliferation in a PD-L1-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Andrea M. Chambers, Jiao Wang, Tram N. Dao, Kyle B. Lupo, Paige Veenhuis, Mitchell G. Ayers, Veronika Slivova, Aaron A. Cohen-Gadol, Sandro Matosevic
Summary: The production of adenosine by CD73 on cancer cells in the tumor microenvironment is an immunosuppressive mechanism. NK cells have limited upregulation of CD73 and it is influenced by cancer type and environment. CD73 overexpression on NK cells responds to the level of CD73 on cancer cells and is enhanced in hypoxia. NK cells in glioblastoma patients show variable CD73 expression and other functional changes.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Sohyun Hwang, Jaejoon Lim, Haeyoun Kang, Ju-Yeon Jeong, Je-Gun Joung, Jinhyung Heo, Daun Jung, Kyunggi Cho, Hee Jung An
Summary: By analyzing immune profiles in tumor tissues, we identified TNFRSF18, TNFSF4, and IL12RB2 as biomarkers that can predict the response of recurrent GBM patients to NK cell therapeutics.
CELL AND BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Koichi Fujisawa, Yuto Nishimura, Akino Sakuragi, Jolien Duponselle, Toshihiko Matsumoto, Naoki Yamamoto, Tomoaki Murata, Isao Sakaida, Taro Takami
Summary: Research has been conducted to develop new medical treatments by simulating environments existing in space, such as zero-gravity. In this study, cell proliferation and gene expression of activated primary human hepatic stellate cells (HHSteCs) under simulated microgravity (SMG) were evaluated. The findings showed slower cell proliferation under SMG conditions, as well as changes in gene expression and oxidative stress. Upstream regulators were activated and cell-permeable inhibitors were inhibited, and cytoskeletal changes were observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Silviya Radoslavova, Antoine Folcher, Thibaut Lefebvre, Kateryna Kondratska, Stephanie Guenin, Isabelle Dhennin-Duthille, Mathieu Gautier, Natalia Prevarskaya, Halima Ouadid-Ahidouch
Summary: This study investigated the role of the Orai1 Ca2+ channel in activated pancreatic stellate cells, revealing its involvement in cell proliferation and TGFβ1 secretion through the AKT signaling pathway. The findings suggest a TGFβ1-induced autocrine positive feedback loop that promotes proliferation through Orai1/AKT-dependent mechanisms.
Article
Allergy
Linda Quatrini, Nicola Tumino, Francesca Besi, Cecilia Ciancaglini, Federica Galaverna, Antonio Giacomo Grasso, Pietro Merli, Franco Locatelli, Paola Vacca, Lorenzo Moretta
Summary: This study investigates the effect of glucocorticoids (GCs) on the development of innate lymphoid cells (ILCs). The results demonstrate that GCs impair lymphoid development while promoting the differentiation of NK cells. Additionally, recipients of hematopoietic stem cell transplantation treated with GCs show a significant reduction in circulating hILCs.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Feifei Guo, Yi Zhang, Ling Bai, Jiuwei Cui
Summary: Cancer stem cells (CSCs) are a small group of cancer cells with stem cell-like properties, which can be used for identifying malignant tumor phenotypes and patients with poor prognosis. Targeting CSCs has been shown to improve the effectiveness of cancer therapies. However, CSCs are resistant to conventional treatment methods such as radiotherapy and chemotherapy, hence the need for more effective anti-CSC therapies.
Article
Multidisciplinary Sciences
Jason Pugh, Lisbeth Guethlein, Peter Parham
Summary: KIR3DL2 is an inhibitory NK cell receptor that recognizes a common epitope of human and pathogen DNA, allowing NK cells to differentiate between self and pathogen DNA and respond accordingly to activate immune responses.
Article
Immunology
Zhaoduan Liang, Wenfang Chen, Yunzhuo Guo, Yuefei Ren, Ye Tian, Wenxuan Cai, Yifeng Bao, Qi Liu, Peng Ding, Yi Li
Summary: In this study, it was found that PD-L1 levels were positively correlated with T-cell apoptosis in cancer patients. PD-L1 inhibited the functions of activated T cells and promoted the generation of Treg cells, thereby facilitating tumor immune escape. This finding provides valuable insights for the development of precision immunotherapy in cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Femke A. I. Ehlers, Niken M. Mahaweni, Timo I. Olieslagers, Gerard M. J. Bos, Lotte Wieten
Summary: The study found that low glucose levels in the bone marrow of multiple myeloma patients did not negatively impact the anti-tumor potential of IL-2 activated NK cells in vitro. High glucose concentrations were shown to diminish NK cell cytotoxicity, suggesting highly activated NK cells could be effective in targeting tumors with reduced glucose environments.
FRONTIERS IN ONCOLOGY
(2021)
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
Akiko Sagara, Kohei Nakata, Sokichi Matsumoto, Weiyu Guan, Tomohiko Shinkawa, Chika Iwamoto, Naoki Ikenaga, Kenoki Ohuchida, Masafumi Nakamura
Summary: The study identified compounds that can suppress PSC activation by targeting the 'neuroactive ligand-receptor interaction' pathway, leading to disruption of tumor-stromal interaction. Among these compounds, duloxetine was found to have this suppressive effect.
