Article
Oncology
Boheng Li, Qidi Zhou, Qin Wan, Xuan Qiao, Shangying Chen, Jianbiao Zhou, Zhijun Wuxiao, Lei Luo, Siok-Bian Ng, Jieping Li, Wee-Joo Chng
Summary: This study identifies TRIP12 as an E3 ligase that triggers polyubiquitination of EZH2, leading to its stabilization and promoting ENKTL cell migration. The TRIP12-EZH2 axis can be regulated by cytoplasmic HSP60 and targeted by dexamethasone treatment.
CLINICAL EPIGENETICS
(2023)
Article
Biochemistry & Molecular Biology
Jianbiao Zhou, Sabrina Hui-Min Toh, Tze King Tan, Kalpnaa Balan, Jing Quan Lim, Tuan Zea Tan, Sinan Xiong, Yunlu Jia, Siok-Bian Ng, Yanfen Peng, Anand D. Jeyasekharan, Shuangyi Fan, Soon Thye Lim, Chin-Ann Johnny Ong, Choon Kiat Ong, Takaomi Sanda, Wee-Joo Chng
Summary: This study identified several super-enhancers (SEs) associated with key transcription factor (TF) genes in extranodal natural killer/T-cell lymphoma (NKTL), including a novel SE named TOX2. Overexpression of TOX2 was found to be associated with worse survival in NKTL patients. Modulating the expression of TOX2 affected the proliferation, survival, and colony formation ability of NKTL cells. Furthermore, a downstream effector of TOX2-mediated oncogenesis, PRL-3, was identified and validated.
Article
Gastroenterology & Hepatology
Olga A. Mareninova, Dustin L. Dillon, Carli J. M. Wightman, Iskandar Yakubov, Toshimasa Takahashi, Herbert Y. Gaisano, Keith Munson, Masaki Ohmuraya, David Dawson, Ilya Gukovsky, Anna S. Gukovskaya
Summary: The study reveals the significant role of Rab9 in regulating autophagy in pancreatic diseases. Overexpression of Rab9 stimulates noncanonical autophagy while inhibiting canonical autophagy, exacerbating pancreatitis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Jian Zhong, Xuesong Yang, Junju Chen, Kejun He, Xinya Gao, Xujia Wu, Maolei Zhang, Huangkai Zhou, Feizhe Xiao, Lele An, Xiuxing Wang, Yu Shi, Nu Zhang
Summary: This study revealed that the overexpression of EZH2-92aa in Glioblastoma leads to immune evasion of the tumor cells from NK cells. EZH2-92aa directly binds and represses the transcription of MICA/B, and indirectly represses ULBP transcription by stabilizing EZH2. Knockdown of EZH2-92aa enhances NK cell-mediated eradication of GSCs and synergizes with anti-PD1 therapy.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Annelisa M. Cornel, Ester Dunnebach, Damon A. Hofman, Sanjukta Das, Satyaki Sengupta, Femke van den Ham, Judith Wienke, Josephine G. M. Strijker, Denise A. M. H. van den Beemt, Anke H. W. Essing, Bianca Koopmans, Sem A. G. Engels, Vania Lo Presti, Celina S. Szanto, Rani E. George, Jan J. Molenaar, Sebastiaan van Heesch, Miranda P. Dierselhuis, S. Nierkens
Summary: This study explores the potential of combining immunotherapy with histone deacetylase inhibitors (HDACi) to enhance T cell-driven and NK cell-driven immune responses in high-risk neuroblastoma (HR-NBL). Screening drug repurposing libraries, the researchers identified compounds that upregulated major histocompatibility complex class I (MHC-I) surface expression in NBL cells. Treatment with HDACi enhanced the cytotoxic capacity of tumor-specific T cells against NBL in vitro and increased the expression of factors regulating T cell and NK cell cytotoxicity. The findings suggest a promising strategy to enhance immune responses in patients with HR-NBL through (immuno)therapy and HDACi.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Weili Xue, Mingzhi Zhang
Summary: NKTCL is a highly invasive subtype of lymphoma with current treatment methods having drawbacks. However, immunotherapy has shown promising results, including targeted antibodies, checkpoint inhibitors, and the role of IL10. Cellular immunotherapy with engineered cytotoxic T lymphocytes also presents potential therapeutic strategies.
CANCER BIOLOGY & MEDICINE
(2021)
Review
Oncology
Xiao-Peng Tian, Yi Cao, Jun Cai, Yu-Chen Zhang, Qi-Hua Zou, Jin-Ni Wang, Yu Fang, Jia-Hui Wang, Song-Bin Guo, Qing-Qing Cai
Summary: The increasing use of high-throughput screening has greatly advanced our knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL) and revolutionized its treatment. Asparaginase-containing regimens have significantly improved survival outcomes in NKTCL patients. Novel treatment strategies, including targeted antibodies, immune checkpoint inhibitors, and chimeric antigen receptor T cells, are currently being developed for NKTCL and show promising potential for future use.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Adam Nelson, Simon Gebremeskel, Brian D. Lichty, Brent Johnston
Summary: The combination of NKT cell activation therapy, oncolytic virotherapy with VSV-IL-15, and PD-1 blockade has been shown to enhance tumor control in pancreatic cancer, providing a promising treatment strategy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cardiac & Cardiovascular Systems
Masashi Sada, Shouji Matsushima, Masataka Ikeda, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Tomonori Tadokoro, Nobuyuki Enzan, Taishi Yamamoto, Hiroko Deguchi Miyamoto, Yoshitomo Tsutsui, Ryo Miyake, Daiki Setoyama, Dongchon Kang, Tomomi Ide, Hiroyuki Tsutsui
Summary: This study found that activation of iNKT cells attenuated Doxorubicin-induced cardiomyocyte death and cardiac dysfunction. This effect may be mediated through increased interferon-γ and phosphorylation of signal transducers and activators of transcription 1 and extracellular signal-regulated kinase.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Cell Biology
Alastair Davies, Shaghayegh Nouruzi, Dwaipayan Ganguli, Takeshi Namekawa, Daksh Thaper, Simon Linder, Fatih Karaoglanoglu, Meltem E. Omur, Soojin Kim, Maxim Kobelev, Sahil Kumar, Olena Sivak, Chiara Bostock, Jennifer Bishop, Marlous Hoogstraat, Amina Talal, Suzan Stelloo, Henk van der Poel, Andries M. Bergman, Musaddeque Ahmed, Ladan Fazli, Haojie Huang, Wayne Tilley, David Goodrich, Felix Y. Feng, Martin Gleave, Housheng Hansen He, Faraz Hach, Wilbert Zwart, Himisha Beltran, Luke Selth, Amina Zoubeidi
Summary: The study demonstrates that prostate cancer can transition to a high-plasticity state in response to potent androgen receptor antagonism, maintaining AR activity and rerouting transcriptional activity through changes in chromatin architecture. This reprogramming is mediated by EZH2 and favors stem cell and neuronal gene networks, highlighting the potential for reversing treatment resistance in prostate cancer.
NATURE CELL BIOLOGY
(2021)
Article
Medicine, General & Internal
Julio Cruz, Daniela Vargas, Annelisse Goecke, Maria Luisa Molina
Summary: This case describes a male patient with nasal-type extranodal NK/T-cell lymphoma presenting with hoarseness, weight loss, and dyspnea. Immunohistochemistry is crucial for the diagnosis of this condition.
Article
Oncology
Ziyuan Shen, Xicheng Chen, Cai Sun, Tianyi Lu, Yuye Shi, Hao Zhang, Jingjing Ye, Ling Wang, Taigang Zhu, Yuqing Miao, Xudong Zhang, Liang Wang, Guoqi Cai, Wei Sang
Summary: The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different, with nasal forms patients having superior overall survival (OS) than nonnasal patients, especially in the era of asparaginase.
Article
Medicine, General & Internal
Jiazhuo Wu, Cunzhen Shi, Hongwen Li, Wenting Song, Shuo Huang, Jianxiang Zhang, Wencai Li, Zhaoming Li, Mingzhi Zhang
Summary: PARP inhibitors have been shown to effectively treat natural killer/T cell lymphoma (NKTCL) by inhibiting cell proliferation, promoting apoptosis, and inducing cell cycle arrest. The combination of PARP inhibitors and cisplatin demonstrated synergistic effects both in vitro and in vivo. LMO2 deficiency reduced the sensitivity of NKTCL cells to PARP inhibitors.
Article
Medicine, General & Internal
Yi Duan, Juan Huang, Johannes Haybaeck, ZhiHui Yang
Summary: Primary extranodal natural killer (NK)/T-cell lymphoma (ENKTL) rarely occurs in childhood and adolescence, especially in the gastrointestinal (GI) tract. It is important to consider ENKTL in the differential diagnosis for patients with GI symptoms, and to differentiate it from GI T-cell lymphomas through morphology and immunohistochemistry. This case emphasizes the need for increased awareness and timely diagnosis of ENKTL in the GI tract in children.
Article
Immunology
Guangwei Cui, Akihiro Shimba, Jianshi Jin, Taisaku Ogawa, Yukiko Muramoto, Hitoshi Miyachi, Shinya Abe, Takuma Asahi, Shizue Tani-Ichi, Johannes M. Dijkstra, Yayoi Iwamoto, Kirill Kryukov, Yuanbo Zhu, Daichi Takami, Takahiro Hara, Satsuki Kitano, Yan Xu, Hajime Morita, Moyu Zhang, Lynn Zreka, Keishi Miyata, Takashi Kanaya, Shinya Okumura, Takashi Ito, Etsuro Hatano, Yoshimasa Takahashi, Hiroshi Watarai, Yuichi Oike, Tadashi Imanishi, Hiroshi Ohno, Toshiaki Ohteki, Nagahiro Minato, Masato Kubo, Georg A. Hollander, Hideki Ueno, Takeshi Noda, Katsuyuki Shiroguchi, Koichi Ikuta
Summary: This study reveals a circulating subset of iNKT cells, C2 iNKT cells, with NK cell-like properties distinct from conventional tissue-resident iNKT cells. C2 iNKT cells protect against tumor metastasis and promote antiviral immune responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Cell Biology
Beiping Zhong, Bing Cheng, Xiaoming Huang, Qian Xiao, Zhitong Niu, Yu-feng Chen, Qiang Yu, Wenyu Wang, Xiao-Jian Wu
Summary: Cancer-associated fibroblasts (CAFs) play a crucial role in colorectal cancer (CRC) metastasis by inducing the expression of Leucine Rich Alpha-2-Glycoprotein 1 (LRG1), which promotes CRC migration and invasion through epithelial-mesenchymal transition (EMT). The CAFs-mediated IL-6-STAT3-LRG1 axis is responsible for the up-regulation of LRG1 in CRC, and higher LRG1 expression predicts poor clinical outcomes, especially distant metastasis free survival in CRC patients.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Ioanna Xagoraris, Pedro Farrajota Neves da Silva, Georgia Kokaraki, Konstantina Stathopoulou, Bjoern Wahlin, Anders Osterborg, Nikolas Herold, Siok-Bian Ng, L. Jeffrey Medeiros, Elias Drakos, Birgitta Sander, George Z. Rassidakis
Summary: The expression of STING protein is restricted to T-cell and NK-cell lymphomas, and it has potential immunotherapeutic implications. These findings provide a new target and strategy for the treatment of lymphomas.
Review
Oncology
Susan Swee-Shan Hue, Siok-Bian Ng, Shi Wang, Soo-Yong Tan
Summary: The intestinal immune system is made up of innate lymphoid cells and various T-cell subsets, which play important roles in immune responses and can also be involved in the development of lymphoma. Understanding the different cell types and their functions in the gastrointestinal tract is crucial for studying and treating related diseases.
Article
Multidisciplinary Sciences
Li-Teng Ong, Wee Chyan Lee, Shijun Ma, Gokce Oguz, Zhitong Niu, Yi Bao, Mubaraka Yusuf, Puay Leng Lee, Jian Yuan Goh, Panpan Wang, Kylie Su Mei Yong, Qingfeng Chen, Wenyu Wang, Adaikalavan Ramasamy, Dave S. B. Hoon, Henrik J. Ditzel, Ern Yu Tan, Soo Chin Lee, Qiang Yu
Summary: In this study, we discovered that IF‑β is highly expressed in HER2(+) breast cancer and inhibits the malignant characteristics of cancer cells by regulating the AKT signaling pathway and XBP1 activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shijun Ma, Yue Zhao, Wee Chyan Lee, Li-Teng Ong, Puay Leng Lee, Zemin Jiang, Gokce Oguz, Zhitong Niu, Min Liu, Jian Yuan Goh, Wenyu Wang, Matias A. Bustos, Sidse Ehmsen, Adaikalavan Ramasamy, Dave S. B. Hoon, Henrik J. Ditzel, Ern Yu Tan, Qingfeng Chen, Qiang Yu
Summary: This study reveals that hypoxia-induced epigenetic suppression of effector gene expression leads to dysfunction of T and NK cells, resulting in resistance to anti-PD1 blockade in triple negative breast cancer. Targeting hypoxia and the associated epigenetic machinery can reverse immune effector dysfunction and overcome immune resistance.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jianfeng Chen, Jing Han Hong, Yulin Huang, Shini Liu, Jiaxin Yin, Peng Deng, Yichen Sun, Zhaoliang Yu, Xian Zeng, Rong Xiao, Jason Yongsheng Chan, Peiyong Guan, Yali Wang, Peili Wang, Lizhen Liu, Shijun Wen, Qiang Yu, Choon Kiat Ong, Bin-Tean Teh, Ying Xiong, Jing Tan
Summary: This study reveals that EZH2 plays an oncogenic role in ovarian cancer through noncatalytic activity. Inhibition of EZH2 degradation, rather than its catalytic activity, can effectively block ovarian cancer growth and tumor formation. Furthermore, EZH2 has extensive occupancy at promoters independent of PRC2 and can upregulate IDH2 to promote metabolic rewiring and contribute to ovarian cancer growth.
Correction
Pathology
Arianna Di Napoli, Lori Soma, Leticia Quintanilla-Martinez, Laurence de Leval, Lorenzo Leoncini, Alberto Zamo, Siok-Bian Ng, Sarah L. Ondrejka, Fina Climent, Andrew Wotherspoon, Stefan Dirnhofer
Review
Pathology
Leticia Quintanilla-Martinez, Camille Laurent, Lorinda Soma, Siok-Bian Ng, Fina Climent, Sarah L. L. Ondrejka, Alberto Zamo, Andrew Wotherspoon, Laurence de Leval, Stefan Dirnhofer, Lorenzo Leoncini
Summary: The 2022 European Association for Haematopathology/Society for Hematopathology workshop in Florence, Italy discussed emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs). The session focused on newly recognized diseases and their diagnostic challenges. Topics included high-grade/large B-cell lymphoma with 11q aberration (HG/LBCL-11q), LBCL with IRF4 rearrangement (LBCL-IRF4), primary bone diffuse large B-cell lymphoma (PB-DLBCL), and B-acute lymphoblastic leukemia (B-ALL) with IGH::MYC translocation.
Review
Pathology
Alberto Zamo, Michiel van den Brand, Fina Climent, Laurence de Leval, Stefan Dirnhofer, Lorenzo Leoncini, Siok-Bian Ng, Sarah L. Ondrejka, Leticia Quintanilla-Martinez, Lorinda Soma, Andrew Wotherspoon
Summary: Session 3 of the lymphoma workshop at the joint meeting of the European Association for Haematopathology and the Society for Hematopathology discussed splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas. The case review emphasized the challenges in diagnosing marginal zone lymphomas, including distinguishing between different types and the need for molecular studies to establish a final diagnosis. The workshop also addressed the overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma.
Review
Pathology
Sarah L. Ondrejka, Catalina Amador, Fina Climent, Siok-Bian Ng, Lorinda Soma, Alberto Zamo, Stefan Dirnhofer, Leticia Quintanilla-Martinez, Andrew Wotherspoon, Lorenzo Leoncini, Laurence de Leval
Summary: Follicular helper T-cell lymphomas (TFH lymphomas), including their morphologic spectrum and subtypes, were discussed at the EA4HP/SH 2022 meeting. The relationship between TFH lymphoma and clonal hematopoiesis was highlighted, as well as the distinction between TFH lymphoma and PTCL, NOS. The challenges of differentiating TFH lymphoma from other established lymphoma types were presented, and the importance of immunophenotyping and next-generation sequencing in understanding and classifying TFH lymphomas was emphasized.
Correction
Pathology
Alberto Zamo, Michiel van den Brand, Fina Climent, Laurence de Leval, Stefan Dirnhofer, Lorenzo Leoncini, Siok-Bian Ng, Sarah L. Ondrejka, Leticia Quintanilla-Martinez, Lorinda Soma, Andrew Wotherspoon
Article
Pathology
Arianna Di Napoli, Lori Soma, Leticia Quintanilla-Martinez, Laurence de Leval, Lorenzo Leoncini, Alberto Zamo, Siok-Bian Ng, Sarah L. Ondrejka, Fina Climent, Andrew Wotherspoon, Stefan Dirnhofer
Summary: The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session discussed various disease entities related to cavity-based lymphomas, including primary effusion lymphomas, HHV8-negative effusion-based lymphomas, and fibrin-associated diffuse large B-cell lymphoma, among others. The workshop focused on understanding the challenges in classifying and diagnosing specific subtypes, such as ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. The case submissions provided valuable insights into the diagnosis, classification, and prognosis of these lymphomas.
Review
Cell Biology
Bing Cheng, Qiang Yu, Wenyu Wang
Summary: Extensive studies in the last decade have shown that the tumor microenvironment (TME) is crucial in cancer development and therapeutic resistance. Within the TME, communication among tumor cells, stromal cells, immune cells, and noncellular components determines the fate of the tumor. Cancer-associated fibroblasts (CAFs), a common component, play pivotal roles in tumorigenesis, tumor progression, therapeutic response, and tumor immunity. Understanding the function of the TME, especially CAFs, is essential in tumor therapy.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Oncology
Wenyu Wang, Bing Cheng, Qiang Yu
Summary: The seed and soil concept has revolutionized cancer treatment in the past decade. The interaction between cancer cells and stromal cells, particularly cancer-associated fibroblasts (CAFs), plays a significant role in tumor progression and therapeutic resistance. Targeting CAFs is an emerging and promising strategy for anticancer therapies.
CANCER DRUG RESISTANCE
(2022)
Article
Medicine, Research & Experimental
Peng Deng, Zining Wang, Jinghong Chen, Shini Liu, Xiaosai Yao, Shaoyan Liu, Lizhen Liu, Zhaoliang Yu, Yulin Huang, Zhongtang Xiong, Rong Xiao, Jiuping Gao, Weiting Liang, Jieping Chen, Hui Liu, Jinghan Hong, Jason Yongsheng Chan, Peiyong Guan, Jianfeng Chen, Yali Wang, Jiaxin Yin, Jundong Li, Min Zheng, Chao Zhang, Penghui Zhou, Tiebang Kang, Bin Tean Teh, Qiang Yu, Zhixiang Zuo, Qingping Jiang, Jihong Liu, Ying Xiong, Xiaojun Xia, Jing Tan
Summary: In this study, RAD21 overexpression in ovarian cancer was found to be inversely correlated with IFN signature gene expression. RAD21 was shown to directly interact with YAP/TEAD4 and recruit NuRD complex to suppress IFN signaling. The study also demonstrated that RAD21 ablation enhanced the efficacy of anti-PD-1 treatment, suggesting RAD21 as a potential target and biomarker for precision immunotherapy in ovarian cancer.
JOURNAL OF CLINICAL INVESTIGATION
(2022)