Article
Chemistry, Multidisciplinary
Suyeon Kim, Roun Heo, Seok Ho Song, Kwon-Ho Song, Jung Min Shin, Se Jin Oh, Hyo-Jung Lee, Jo Eun Chung, Jae Hyung Park, Tae Woo Kim
Summary: Foreignization of tumor cells by delivering a non-self foreign antigen into tumors is an effective strategy for tumor rejection. However, immune-suppressive factors in the tumor microenvironment limit the immune response against tumor antigens. Blocking PD-L1 on both tumor cells and dendritic cells can enhance the induction of tumor-reactive T cells and strengthen the anti-tumor immunity initiated by tumor-foreignization.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Yufan Qiu, Yi Yang, Riyao Yang, Chunxiao Liu, Jung-Mao Hsu, Zhou Jiang, Linlin Sun, Yongkun Wei, Chia-Wei Li, Dihua Yu, Jin Zhang, Mien-Chie Hung
Summary: The study reveals that PD-1 can be secreted in an exosomal form by activated T cells and interact remotely with PD-L1. This interaction can attenuate the suppression of tumor-specific cytotoxic T cell activity by PD-L1, restoring tumor surveillance.
Article
Multidisciplinary Sciences
Qiang Zhu, Hongxing Wang, Siyuan Chai, Liang Xu, Bingyi Lin, Wen Yi, Liming Wu
Summary: Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) play a role in T cell-mediated immune response against tumors. The regulation of cell surface PD-L1 is not well understood, but it is shown in this study that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc). Inhibition of O-GlcNAc activates T cell-mediated anti-tumor immunity and combining it with PD-L1 antibody enhances the immune response. A competitive peptide inhibitor of HGS glycosylation decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. This study reveals a link between O-GlcNAc and tumor immune evasion, providing strategies for improving PD-L1-mediated immune checkpoint blockade therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Houhong Wang, Amao Tang, Yayun Cui, Huihui Gong, Heng Li
Summary: LRPPRC regulates PD-L1 expression through m(6)A modification in HCC, leading to immune evasion. Inhibition of LRPPRC can suppress tumor growth and enhance anti-tumor immunity by downregulating PD-L1 expression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Tina Daunke, Silje Beckinger, Sascha Rahn, Sandra Kruger, Steffen Heckl, Heiner Schafer, Daniela Wesch, Christian Pilarsky, Markus Eckstein, Arndt Hartmann, Christoph Rocken, Anna Maxi Wandmacher, Susanne Sebens
Summary: In pancreatic ductal adenocarcinoma (PDAC), tumor-associated macrophages express PD-L1 while PDAC cells do not. PD-L1 expression is high at the tumor invasion front between tumor-associated macrophages and CD8+ T cells. Treatment with immune checkpoint inhibitors (ICI) does not enhance the activation and cytotoxicity of CD8+ T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Qian Li, Jingjing Han, Yonglin Yang, Yu Chen
Summary: Hepatocellular carcinoma (HCC) has a high prevalence and mortality rate worldwide. In recent years, immunotherapy using immune checkpoint inhibitors, particularly targeting the PD-1/PD-L1 axis, has brought fundamental changes to the treatment of advanced HCC. However, challenges remain and combination therapy may be a better option to improve the low remission rate.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Man Shang, Huijie Yang, Ran Yang, Tao Chen, Yuan Fu, Yeyi Li, Xianlong Fang, Kangjian Zhang, Jianju Zhang, Hui Li, Xueping Cao, Jinfa Gu, Jianwen Xiao, Qi Zhang, Xinyuan Liu, Qiujing Yu, Ting Wang
Summary: The study reveals a crucial role of MTHFD2 in promoting PD-L1 expression in tumors and facilitating tumorigenesis, potentially through the folate cycle and O-GlcNAcylation.
NATURE COMMUNICATIONS
(2021)
Review
Medical Laboratory Technology
Yamin Liang, Lu Li, Yanmei Chen, Jinyan Xiao, Dangheng Wei
Summary: The PD-1/PD-L1 pathway is crucial in immune responses and cancer therapy, but may accelerate the progression of atherosclerosis in some patients.
CLINICA CHIMICA ACTA
(2021)
Article
Oncology
Stella A. Martomo, Jeegar Patel
Summary: KD033 is an immunocytokine composed of an anti-human-PD-L1 antibody and IL-15/IL-15 receptor sushi-domain complex. It has shown efficacy in tumor models resistant to anti-PD-1/PD-L1 checkpoint blockers. KD033 was effective in both low and high PD-L1-expressing tumors. It reproduced the anti-tumor efficacy in syngeneic models and induced changes in transcriptomic profiles and immune-related genes.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Alexander Stein, Donjete Simnica, Christoph Schultheiss, Rebekka Scholz, Joseph Tintelnot, Eray Goekkurt, Lisa von Wenserski, Edith Willscher, Lisa Paschold, Markus Sauer, Sylvie Lorenzen, Jorge Riera-Knorrenschild, Reinhard Depenbusch, Thomas J. Ettrich, Steffen Doerfel, Salah-Eddin Al-Batran, Meinolf Karthaus, Uwe Pelzer, Lisa Waberer, Axel Hinke, Marcus Bauer, Chiara Massa, Barbara Seliger, Claudia Wickenhauser, Carsten Bokemeyer, Susanna Hegewisch-Becker, Mascha Binder
Summary: In MSS mCRC patients, immune checkpoint blockade is ineffective, but combining avelumab with standard treatment appears safe and feasible. PD-L1 mutations mediate subclonal immune escape to avelumab, particularly in patients expressing high-affinity Fc gamma R3a, leading to enhanced T cell killing and limiting subclonal expansion. Further trials evaluating the addition of avelumab in this patient subgroup are warranted.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Gastroenterology & Hepatology
Feng Zhang, Keshu Hu, Wenfeng Liu, Bing Quan, Miao Li, Shenxin Lu, Rongxin Chen, Zhenggang Ren, Xin Yin
Summary: This study investigates the role of ID1/Myc signaling on immune evasion in oxaliplatin-resistant HCC. The results show that increased ID1/Myc expression is correlated with PD-L1 up-regulation and PMN-MDSC accumulation. Knockdown of Myc sensitizes oxaliplatin-resistant HCC cells to oxaliplatin and decreases PMN-MDSCs while increasing IFN-gamma(+)/CD8(+) T cells.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Clemens Hinterleitner, Jasmin Straehle, Elke Malenke, Martina Hinterleitner, Melanie Henning, Marco Seehawer, Tatjana Bilich, Jonas Heitmann, Martina Lutz, Sven Mattern, Sophia Scheuermann, Marius Horger, Stefanie Maurer, Juliane Walz, Falko Fend, Rupert Handgretinger, Christian Seitz, Bettina Weigelin, Stephan Singer, Helmut Salih, Oliver Borst, Hans-Georg Kopp, Lars Zender
Summary: This study demonstrates that platelet-derived PD-L1 can serve as a prognostic and predictive biomarker in non-small cell lung cancer patients, playing a role in tumor immune evasion and affecting T cell function. An algorithm was developed to calculate the adjusted PD-L1 payload of platelets (pPD-L1(Adj.)), which showed superior predictive ability for therapy response compared to standard histological PD-L1 quantification.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Li You, Xu Wang, Wenda Wu, Eugenie Nepovimova, Qinghua Wu, Kamil Kuca
Summary: Trichothecene mycotoxins have a strong immunosuppressive effect and are closely related to immune evasion mechanisms. Hypoxia and hypoxia-inducible factors (HIFs) play a key role in mediating trichothecenes. HIF-1 alpha inhibits T-2 toxin-mediated immune evasion process by negatively regulating PD-1/PD-L1 signaling.
Article
Cell Biology
Min Lu, Kaixuan Wang, Wenxiang Ji, Yongfeng Yu, Ziming Li, Weiliang Xia, Shun Lu
Summary: FGFR1 activation is positively correlated with PD-L1 transcription in lung squamous cell carcinoma. FGFR1 upregulates PD-L1 expression through YAP, while FGFR1 knockdown decreases tumor growth, reduces immune escape, and induces reactivation of CD8+ T cells. The combination of FGFR1 knockdown and PD-1 blockade synergistically exerts antitumor effects.
CELLULAR IMMUNOLOGY
(2022)
Article
Oncology
Huijie Yang, Min Xue, Peng Su, Yan Zhou, Xin Li, Zhongbo Li, Yan Xia, Chenmiao Zhang, Mingxi Fu, Xiuxia Zheng, Guosheng Luo, Tian Wei, Xinxing Wang, Yinlu Ding, Jian Zhu, Ting Zhuang
Summary: In this study, the tumor-suppressive function of RNF31 in triple negative breast cancer (TNBC) was demonstrated. It was found that RNF31 could regulate the Hippo signaling pathway and its depletion increased TNBC cell proliferation and migration. Clinical data also showed that RNF31 expression was correlated with longer relapse-free survival in TNBC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biology
Anmin Wang, Wanyiin Tao, Jiyu Tong, Juanzi Gao, Jinghao Wang, Gaopeng Hou, Chen Qian, Guorong Zhang, Runzhi Li, Decai Wang, Xingxing Ren, Kaiguang Zhang, Siyuan Ding, Richard A. Flavell, Huabing Li, Wen Pan, Shu Zhu
Summary: The study found that m6A modification plays an antiviral role in the intestinal immune defense against rotavirus infection. Rotavirus infection induces global m6A modifications, and mice lacking the m6A writer enzyme METTL3 show resistance to rotavirus infection. During rotavirus infection, IRF7 is identified as a primary m6A target, and loss of METTL3 enhances Irf7 mRNA stability and IFN expression. Deficiency in IRF7 attenuates IFN expression and restores susceptibility to rotavirus infection.
Article
Oncology
Zhen Liu, Youqiong Ye, Yizhe Liu, Yanfang Liu, Huifang Chen, Mengting Shen, Zhen Wang, Shenglin Huang, Leng Han, Zhiao Chen, Xianghuo He
Summary: DHX37, a dysregulated RNA helicase in hepatocellular carcinoma (HCC), interacts with PLRG1 to promote cell proliferation and cyclin D1 expression. This cooperative mechanistic interaction contributes to liver cancer progression and improves our understanding of epigenetic and transcriptional dysregulations in HCC mediated by RNA helicases and superenhancers.
Article
Multidisciplinary Sciences
Ting Zhang, Chenbo Ding, Huifang Chen, Jun Zhao, Zhejun Chen, Baiwen Chen, Kaiqiong Mao, Yajuan Hao, Manolis Roulis, Hao Xu, Yuval Kluger, Qiang Zou, Youqiong Ye, Meixiao Zhan, Richard A. Flavell, Hua-Bing Li
Summary: Colonic mucosal barrier dysfunction is a major cause of inflammatory bowel disease (IBD), and m(6)A modification plays a crucial role in maintaining the homeostatic self-renewal of colonic stem cells.
Article
Multidisciplinary Sciences
Chenbo Ding, Hao Xu, Zhibin Yu, Manolis Roulis, Rihao Qu, Jing Zhou, Joonseok Oh, Jason Crawford, Yimeng Gao, Ruaidhri Jackson, Esen Sefik, Simiao Li, Zheng Wei, Mathias Skadow, Zhinan Yin, Xinshou Ouyang, Lei Wang, Qiang Zou, Bing Su, Weiguo Hu, Richard A. Flavell, Hua-Bing Li
Summary: This study found that ALKBH5 and m(6)A modification are involved in the development of γδT cells. Depletion of ALKBH5 leads to an expansion of γδT cells, resulting in enhanced protection against Salmonella typhimurium infection in the gastrointestinal tract. This is attributed to the increased development of γδT cell precursors and the reduced expression of target genes in the Notch signaling pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Qianwen Hu, Tingting Xu, Min Zhang, Heng Zhang, Yongbo Liu, Hua-bing Li, Chiqi Chen, Junke Zheng, Zhen Zhang, Fubin Li, Nan Shen, Wenqian Zhang, Ari Melnick, Chuanxin Huang
Summary: The study reveals that Bach2 protein and transcripts in activated B cells have differential roles in controlling their cell-fate outcomes and the fate of their descendant effector cells.
Article
Cell Biology
Yaohua Zhang, Chengcao Sun, Yajuan Li, Juan Qin, Kaushik Amancherla, Ying Jing, Qingsong Hu, Ke Liang, Zhao Zhang, Youqiong Ye, Lisa A. Huang, Tina K. Nguyen, Sergey D. Egranov, Zilong Zhao, Andrew Wu, Yutao Xi, Jun Yao, Mien-Chie Hung, George A. Calin, Jie Cheng, Bora Lim, Lorenz H. Lehmann, Joe-Elie Salem, Douglas B. Johnson, Michael A. Curran, Dihua Yu, Leng Han, Radbod Darabi, Liuqing Yang, Javid J. Moslehi, Chunru Lin
Summary: This study found that tumor-bearing mice treated with immune checkpoint inhibitors (ICIs) for cancer showed cardiovascular toxicities, including myocarditis and arrhythmia. Female mice were more susceptible to myocarditis. The down-regulation of MANF and HSPA5 in the heart tissue was associated with these cardiac effects.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jialin Mo, Kezhe Tan, Yu Dong, Wenjie Lu, Fang Liu, Yanqing Mei, Hongting Huang, Kewen Zhao, Zhibao Lv, Youqiong Ye, Yujie Tang
Summary: The study identifies SSRP1 as a crucial gene that is directly induced by EWSR1::FLI1 and forms an oncogenic positive feedback loop with it, promoting EwS oncogenesis. The FACT inhibitor CBL0137 effectively disrupts this loop, providing a novel therapeutic strategy for treating EwS.
Article
Multidisciplinary Sciences
Chengcao Sun, Youqiong Ye, Zhi Tan, Yuan Liu, Yajuan Li, Wei Hu, Ke Liang, Sergey D. Egranov, Lisa Angela Huang, Zhao Zhang, Yaohua Zhang, Jun Yao, Tina K. Nguyen, Zilong Zhao, Andrew Wu, Jeffrey R. Marks, Abigail S. Caudle, Aysegul A. Sahin, Jianjun Gao, Seth T. Gammon, David Piwnica-Worms, Jian Hu, Paul J. Chiao, Dihua Yu, Mien-Chie Hung, Michael A. Curran, George A. Calin, Haoqiang Ying, Leng Han, Chunru Lin, Liuqing Yang
Summary: One major obstacle in treating PDAC is its immunoresistant microenvironment. This study identified the importance of Schwann cells in PDAC and their correlation with immune suppressive tumor microenvironment and poor patient outcomes. It was found that the depletion of pancreatic-specific TASc promoted PDAC tumor growth, while depletion of TASc-expressed PVT1 suppressed tumor growth and sensitized PDAC to immunotherapy. The findings highlight the significant roles of TASc in PDAC immune resistance.
Review
Biochemistry & Molecular Biology
Jiachen Zhao, Chenbo Ding, Hua-Bing Li
Summary: T cells derived from hematopoietic stem cells are divided into alpha beta and gamma delta T cells and undergo different developmental processes. The depletion of m(6)A demethylase ALKBH5 specifically leads to an expansion of gamma delta T cells through signaling regulation. This indicates the important role of ALKBH5 and m(6)A modification in the early development of gamma delta T cells.
Article
Biochemistry & Molecular Biology
Qianqian Song, Mingyu Li, Qian Li, Xun Lu, Kun Song, Ziliang Zhang, Jiale Wei, Liang Zhang, Jiacheng Wei, Youqiong Ye, Jinyin Zha, Qiufen Zhang, Qiang Gao, Jiang Long, Xinyi Liu, Xuefeng Lu, Jian Zhang
Summary: Driver mutations play a crucial role in cancer initiation and their identification is important for understanding tumorigenesis and drug development. Mutations at allosteric sites have been associated with protein structure and dynamics. DeepAlloDriver, a deep learning platform, achieves >93% accuracy and precision in predicting driver mutations, and it identified a missense mutation in RRAS2 as a potential allosteric driver of tumorigenesis. This research provides insights into cancer mechanisms and aids in prioritizing therapeutic targets.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Chenbo Ding, Zhibin Yu, Esen Sefik, Jing Zhou, Eleanna Kaffe, Gaoyang Wang, Bin Li, Richard A. Flavell, Weiguo Hu, Youqiong Ye, Hua-Bing Li
Summary: This study identified a T-reg-specific long noncoding RNA called Altre, which plays a role in regulating the mitochondrial function of T-reg cells in the liver of old mice by binding to Yin Yang 1. Deletion of Altre accelerates aging-associated liver pathogenesis.
Letter
Biochemistry & Molecular Biology
Yi He, Yu Dong, Yong Chen, Guanxiong Zhang, Hailun Zhang, Guang Lei, Yanhua Du, Xiang Chen, Youqiong Ye, Hong Liu
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Medicine, Research & Experimental
Zhongqiu Wu, Haiyan Huang, Qiaoqiao Han, Zhilin Hu, Xiao-Lu Teng, Rui Ding, Youqiong Ye, Xiaoyan Yu, Ren Zhao, Zhengting Wang, Qiang Zou
Summary: Research finds that SENP7 can sense oxidative stress, maintain the metabolic state and antitumor functions of CD8+ T cells, with deficient SENP7 cells showing impaired metabolic activity. ROS derived from CD8+ T cells trigger SENP7-mediated PTEN deSUMOylation, promoting PTEN degradation to prevent metabolic defects.
JOURNAL OF CLINICAL INVESTIGATION
(2022)