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
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)
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
Biochemistry & Molecular Biology
Anna Pawlowska, Agnieszka Kwiatkowska, Dorota Suszczyk, Agata Chudzik, Rafal Tarkowski, Bartlomiej Barczynski, Jan Kotarski, Iwona Wertel
Summary: The study highlights the significant role of the PD-1/PD-L1/PD-L2 axis in ovarian cancer pathogenesis, with a focus on the clinical importance of PD-L1/PD-L2 expression in the OC environment. Elevated levels of sPD-L1 in peritoneal fluid were found to be associated with shorter survival in OC patients, indicating a potential hallmark of immune regulation in this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
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
Biochemistry & Molecular Biology
Yang Xia, Wei-Cheng Wang, Wen-Hao Shen, Kun Xu, Yang-Yang Hu, Gao-Hua Han, Yong-Biao Liu
Summary: This study demonstrated that thalidomide inhibits NSCLC angiogenesis and immune evasion by targeting FGD5-AS1. FGD5-AS1 regulates the expression of PD-L1 and VEGFA through the miR-454-3p/ZEB1 axis, affecting the PD-1/PD-L1 checkpoint and exerting anti-tumor effects.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Pharmacology & Pharmacy
Zhiwei Fan, Changyue Wu, Miaomiao Chen, Yongying Jiang, Yuanyuan Wu, Renfang Mao, Yihui Fan
Summary: This article provides a systematic and comprehensive overview of the regulation of PD-L1, from nuclear chromatin reorganization to extracellular presentation. Understanding the regulation of PD-L1/PD-L2 and their regulatory networks can shed light on the development and application of immune checkpoint blockade therapy and combination therapies.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Medicine, Research & Experimental
Tanmoy Mondal, Gururaj N. Shivange, Rachisan G. T. Tihagam, Evan Lyerly, Michael Battista, Divpriya Talwar, Roxanna Mosavian, Karol Urbanek, Narmeen S. Rashid, J. Chuck Harrell, Paula D. Bos, Edward B. Stelow, M. Sharon Stack, Sanchita Bhatnagar, Jogender Tushir-Singh
Summary: Clinical DR5 antibodies activate an unexpected immunosuppressive PD-L1 stabilization pathway, potentially contributing to their limited success in clinics. Targeting the DR5-ROCK1-PD-L1 axis significantly enhances immune effector T-cell function, promotes tumor regression, and improves overall survival in animal models. This insight suggests a potential clinically viable combinatorial strategy to revive solid cancer immunotherapy using death receptor agonism.
EMBO MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Maite Duhalde Vega, Daniela Olivera, Gustavo Gastao Davanzo, Mauricio Bertullo, Veronica Noya, Gabriela Fabiano de Souza, Stefanie Primon Muraro, Icaro Castro, Ana Paula Arevalo, Martina Crispo, German Galliussi, Sofia Russo, David Charbonnier, Florencia Rammauro, Mathias Jeldres, Catalina Alamon, Valentina Varela, Carlos Batthyany, Mariela Bollati-Fogolin, Pablo Oppezzo, Otto Pritsch, Jose Luiz Proenca-Modena, Helder I. Nakaya, Emiliano Trias, Luis Barbeito, Ignacio Anegon, Maria Cristina Cuturi, Pedro Moraes-Vieira, Mercedes Segovia, Marcelo Hill
Summary: This study reveals the correlation between inflammation and dysfunctional T cell responses, showing that manipulating T cells can control certain viral infections. These findings provide new insights for supporting immunotherapy targeting critical viral diseases.
Article
Oncology
Didem Naz Dioken, Ibrahim Ozgul, Irem Yilmazbilek, Mustafa Cengiz Yakicier, Ezgi Karaca, Ayse Elif Erson-Bensan
Summary: Targeting PD-1/PD-L1 in cancer therapy has shown significant therapeutic response, but challenges remain in predicting treatment effectiveness, understanding resistance mechanisms, and identifying additional biomarkers. This study explores the overlooked isoforms of PD-L1 and PD-L2 in breast cancer and other tumors, revealing a unique PD-L1 isoform (PD-L1 Delta 3) that lacks a crucial interaction domain with PD-1. We also find widespread expression of PD-L2, which positively correlates with PD-L1 levels. The high expression of PD-L2 is associated with enriched epithelial-mesenchymal transition (EMT) signature in breast cancer subtypes, suggesting a potential crosstalk between EMT and immune evasion. These findings highlight the importance of utilizing isoform-specific antibodies for PD-L2 and PD-L1 in staining patient tissues for more precise prediction of PD-1/PD-L1 immunotherapy outcomes.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Masanori A. Murayama, Erika Takada, Kenji Takai, Nagisa Arimitsu, Jun Shimizu, Tomoko Suzuki, Noboru Suzuki
Summary: The expression of PD-L1 and PD-L2 in breast cancer cells varies, and nicotine regulates their expression by inhibiting Akt phosphorylation.
Article
Biochemistry & Molecular Biology
Yung-Hung Luo, Yi-Ping Yang, Chian-Shiu Chien, Aliaksandr A. Yarmishyn, Afeez Adekunle Ishola, Yueh Chien, Yuh-Min Chen, Ping-Hsing Tsai, Tzu-Wei Lin, Mong-Lien Wang, Shih-Hwa Chiou
Summary: Lung cancer is the leading cause of death from cancer in Taiwan and worldwide. Immunotherapy has shown promising efficacy in non-small cell lung cancer (NSCLC) by blocking the PD-1/PD-L1 signaling pathway. Circular RNAs (circRNAs) have been identified as potential blood-based biomarkers to monitor the disease progression and immunotherapy efficacy. Hsa_ circ_0000190 was found to interfere with anti-PD-L1 antibody and T-cell activation, leading to immunotherapy resistance and poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Luise Victoria Claass, Christoph Schultheiss, Rebekka Scholz, Lisa Paschold, Donjete Simnica, Volker Heinemann, Sebastian Stintzing, Mascha Binder
Summary: The two most common antibody targeting principles in oncology are direct antitumor effects and the release of antitumor T cell immunity through immune checkpoint blockade. This study confirms that the targeting of checkpoint molecules on tumor cells can also lead to direct tumor cell killing. It also identifies PD-L1 position 88 as a hotspot residue that critically regulates PD-L1 cell surface expression in the context of immune checkpoint blockade.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Qiang Chen, Yilin Hong, Shihe Weng, Peng Guo, Bei Li, Yong Zhang, Chundong Yu, Shicong Wang, Pingli Mo
Summary: PZH can inhibit the proliferation of CRC and suppress its immune escape by down-regulating PCNA and Cyclin D1 expression and inhibiting PD-L1 levels. It also increases the infiltration of CD8(+) T cells in tumor tissues.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Dirk Schuermann, Deanne Jackson Rudd, Andrea Schaeffer, Inge De Lepeleire, Evan J. Friedman, Martine Robberechts, Saijuan Zhang, Yang Liu, Bhargava Kandala, Christian Keicher, Martin Daumer, Jorg Hofmann, Jay A. Grobler, S. Aubrey Stoch, Marian Iwamoto, Wendy Ankrom
Summary: MK-8507 is a promising non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. It demonstrated robust antiviral activity, favorable pharmacokinetic properties, and good tolerability in this phase 1 study.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Infectious Diseases
Julia Schneider, Friederike Bachmann, Mira Choi, Lille Kurvits, Marie Luisa Schmidt, Leon Bergfeld, Iris Meier, Marta Zuchowski, Dirk Werber, Joerg Hofmann, Klemens Ruprecht, Kai-Uwe Eckardt, Terry C. Jones, Christian Drosten, Victor Max Corman
Summary: The West Nile Virus (WNV) infections are increasingly detected in central Europe, with the first mosquito-borne autochthonous human infection detected in Germany in 2019. This case study described a WNV-encephalitis case in a 33-year-old kidney transplant recipient, which highlighted the importance of considering WNV in cases of meningoencephalitis, especially in immunocompromised patients. Proper education, communication, and revised diagnostic strategies are essential in raising awareness and detecting future WNV infections.
TRANSBOUNDARY AND EMERGING DISEASES
(2022)
Article
Multidisciplinary Sciences
C-Patrick Papp, Paula Biedermann, Dominik Harms, Bo Wang, Marianne Kebelmann, Mira Choi, Johannes Helmuth, Victor M. Corman, Andrea Thuermer, Britta Altmann, Patrycja Klink, Joerg Hofmann, C-Thomas Bock
Summary: The awareness of hepatitis E virus (HEV) has significantly increased in the last decade due to its unexpectedly high prevalence in high-income countries. However, the spectrum and occurrence of HEV-3 variants are underreported. A new molecular approach utilizing long-range PCR and next-generation and third-generation sequencing was used to gain in-depth insights into the viral population and to characterize HEV-3 genomes. The approach identified a variant with multiple insertions in the HVR-domain, which is the first of its kind recognized.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Medicine, General & Internal
Jorg Hofmann, Martin Loyen, Mirko Faber, Detlev H. Kruger
Summary: In addition to the well-known clinical symptoms of hantavirus disease, unusual neurological changes are also focused on. Rapid IgM tests are valuable for initial diagnosis and supportive measures are the only available therapeutic approaches. Molecular genetic analysis allows characterization of different hantavirus strains. The prevalent human pathogenic hantaviruses in Germany are Puumala virus and Dobrava-Belgrade virus. Ingestion of virus-containing materials can also cause hantavirus infection. Human-to-human transmission of South American hantaviruses is not confirmed. Hantaviruses have been detected in shrews, moles, and bats.
DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
(2022)
Article
Infectious Diseases
Martin Moeckel, Myrto Bolanaki, Joerg Hofmann, Angela Stein, Jennifer Hitzek, Fabian Holert, Antje Fischer-Rosinsk, Anna Slagman
Summary: This study recruited patients in need of urgent inpatient treatment for POC-PCR testing and found that the diagnostic accuracy reached 100%. Compared to the traditional central laboratory PCR testing, the results of POC-PCR testing were available significantly earlier, and the process was successfully integrated into the laboratory information system.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2022)
Article
Immunology
Carolin Otto, Helena Radbruch, Diana Wilken, Tatjana Lietzow, Katja Steinhagen, Evelin Grage-Griebenow, Ann-Christin Von Brunneck, Sven Jarius, Joerg Hofmann, Florence Pache, Klemens Ruprecht
Summary: This study analyzed the intrathecal production of EBV antibodies in patients with PCNS-PTLD and NINDs. The results suggest that the production of VCA-IgG and VCA-IgA in the cerebrospinal fluid may be common in PCNS-PTLD and could potentially aid in the diagnosis of this disease.
JOURNAL OF NEUROIMMUNOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Christina Princk, Stephan Drewes, Kristin M. Meyer-Schlinkmann, Marion Saathoff, Florian Binder, Jona Freise, Beate Tenner, Sabrina Weiss, Jorg Hofmann, Jutta Esser, Martin Runge, Jens Jacob, Rainer G. Ulrich, Johannes Dreesman
Summary: In a small company in Germany, five employees contracted hantavirus infections in late 2017. Through investigations and serological testing, it was found that these infections were closely related to the bank vole population near the company. This investigation highlights the importance of a One Health approach in revealing the origin of hantavirus disease clusters.
ZOONOSES AND PUBLIC HEALTH
(2022)
Article
Medicine, General & Internal
Simon Ronicke, Bilgin Osmanodja, Klemens Budde, Annika Jens, Charlotte Hammett, Nadine Koch, Bianca Zukunft, Friederike Bachmann, Mira Choi, Ulrike Weber, Bettina Eberspaecher, Joerg Hofmann, Fritz Grunow, Michael Mikhailov, Fabian Halleck, Eva Schrezenmeier
Summary: The immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, and repeated vaccinations show a decrease in antibody levels over time with high interindividual variability. Different assays may produce divergent results, suggesting the need for repeated sampling and shorter vaccination intervals in these patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Caroline Zoellner, Joerg Hofmann, Katrin Lutz, Frank Tacke, Muenevver Demir
Summary: This study describes the first 48 weeks of bulevirtide therapy in eight patients, showing a favorable safety profile and significant biochemical and virological response in the majority of patients.
LIVER INTERNATIONAL
(2022)
Article
Immunology
Gunther Schoenrich, Mohammed O. Abdelaziz, Martin J. Raftery
Summary: Multiple Sclerosis (MS) is an autoimmune disease characterized by inflammation and demyelination of nerve cells. Epstein-Barr virus (EBV) infection greatly increases the risk of subsequent MS. EBV induces both human interleukin-10 (IL-10) and a similar molecule, encoded by the virus (ebvIL-10), which work together to establish latent infection in B cells and balance the function of antiviral T cells. If the set point is too high, MS may be induced as collateral damage.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Immunology
Gary Whitlock, Jon Clark, Vicky Tittle
Letter
Immunology
Gary Whitlock, Jon Clark, Vicky Tittle, Dean St Collaborative Grp Dean St Collaborative Grp
Article
Microbiology
Eva Wu, Nadine Koch, Friederike Bachmann, Marten Schulz, Evelyn Seelow, Ulrike Weber, Johannes Waiser, Fabian Halleck, Mirko Faber, Claus-Thomas Bock, Kai-Uwe Eckardt, Klemens Budde, Joerg Hofmann, Peter Nickel, Mira Choi
Summary: There is a significant risk of hepatitis E virus (HEV) infection in kidney and combined kidney transplant recipients, especially those who receive intense immunosuppression. Some patients achieve remission without further treatment, while others require retreatment or cannot clear the virus. HEV infection is associated with the consumption of undercooked pork or pork products.
Article
Public, Environmental & Occupational Health
Patrycja Klink, Dominik Harms, Britta Altmann, Yvonne Doerffel, Ulrike Morgera, Steffen Zander, C. Thomas Bock, Joerg Hofmann
Summary: This study describes the molecular characterization of a rabbit hepatitis E virus (raHEV) strain isolated from an immunocompromised heart-transplanted patient with chronic HEV infection. After successful ribavirin (RBV) treatment, the patient tested HEV positive again and received a second RBV therapy cycle. Sequence analysis showed that the raHEV strain had the highest similarity to a Chinese raHEV and had a phylogenetic relationship with a raHEV strain from a French patient. The results highlight the role of rabbits as potential sources of HEV infection and emphasize the importance of a one health concept in understanding HEV epidemiology and developing prevention and control tools.
Article
Microbiology
Marina Bondareva, Lisa Budzinski, Pawel Durek, Mario Witkowski, Stefan Angermair, Justus Ninnemann, Jakob Kreye, Philine Letz, Marta Ferreira-Gomes, Iaroslav Semin, Gabriela Maria Guerra, S. Momsen Reincke, Elisa Sanchez-Sendin, Selin Yilmaz, Toni Sempert, Gitta Anne Heinz, Caroline Tizian, Martin Raftery, Guenther Schoenrich, Daria Matyushkina, Ivan Smirnov, Vadim M. Govorun, Eva Schrezenmeie, Anna-Luisa Stefanski, Thomas Doerner, Silvia Zocche, Edoardo Viviano, Nele Klement, Katharina Johanna Sehmsdorf, Alexander Lunin, Hyun-Dong Chang, Marina Drutskaya, Liubov Kozlovskaya, Sascha Treskatsch, Andreas Radbruch, Andreas Diefenbach, Harald Pruess, Philipp Enghard, Mir-Farzin Mashreghi, Andrey A. Kruglov
Summary: The commensal microflora induces salivary anti-SARS-CoV-2 Spike IgG antibodies through molecular mimicry, enhancing protective immunity.
CELL HOST & MICROBE
(2023)