Review
Oncology
Xingcheng Yang, Ling Ma, Xiaoying Zhang, Liang Huang, Jia Wei
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases that arise from the bone marrow. Dysregulated immune microenvironment, including the molecules PD-1 and PD-L1, play important roles in the pathogenesis of MDS and AML. However, clinical trials using PD-1/PD-L1 inhibitors have reported mixed responses in patients with these diseases.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Cunte Chen, Ling Xu, Rili Gao, Shunqing Wang, Yuping Zhang, Caixia Wang, Chengwu Zeng, Yangqiu Li
Summary: The study revealed that increased BRD4 expression was associated with poor overall survival in AML patients. Additionally, co-expression of BRD4 with PD-1 or PD-L1 was linked to worse overall survival. The co-expression of BRD4 and PD-L1 was positively correlated with high tumor mutation burden and contributed to poor overall survival in AML patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Laura Jimbu, Oana Mesaros, Alexandra Neaga, Ana Maria Nanut, Ciprian Tomuleasa, Delia Dima, Corina Bocsan, Mihnea Zdrenghea
Summary: Tumor cells promote suppression of host anti-tumor responses by upregulating inhibitory molecules like PD-L1 and producing immunosuppressive cytokines like IL-10. Blocking PD-L1 and IL-10 may be a promising immunotherapeutic approach for AML patients.
Article
Biochemistry & Molecular Biology
Ze-Wei Huang, Xue-Ning Zhang, Ling Zhang, Ling-Ling Liu, Jing-Wen Zhang, Yu-Xiang Sun, Jue-Qiong Xu, Quentin Liu, Zi-Jie Long
Summary: This article discusses the challenges of applying immunotherapy in acute myeloid leukemia (AML) and presents the STAT5-lactate-PD-L1 network, which may help identify which AML patients can benefit from PD-1/PD-L1-based immunotherapy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Chemistry, Medicinal
Laura Jimbu, Oana Mesaros, Cristian Popescu, Alexandra Neaga, Iulia Berceanu, Delia Dima, Mihaela Gaman, Mihnea Zdrenghea
Summary: Checkpoint inhibitors, particularly PD-1/PD-L1 inhibitors, have shown promising results in various solid cancers and hematologic diseases. However, their effectiveness in treating AML is limited, possibly due to disease characteristics and immune system dysregulation, warranting further research for optimal use.
Article
Cell Biology
Mengjun Zhong, Rili Gao, Ruocong Zhao, Youxue Huang, Cunte Chen, Kehan Li, Xibao Yu, Dingrui Nie, Zheng Chen, Xin Liu, Zhuandi Liu, Shaohua Chen, Yuhong Lu, Zhi Yu, Liang Wang, Peng Li, Chengwu Zeng, Yangqiu Li
Summary: The BET inhibitor JQ1 was found to inhibit the expression of PD-1 in T cells and enhance anti-leukemia immunity. JQ1 also suppressed the growth of AML cells and prolonged survival in mouse models.
CELL DEATH & DISEASE
(2022)
Review
Immunology
Huizhen Cao, Tianyu Wu, Xue Zhou, Shuyang Xie, Hongfang Sun, Yunxiao Sun, Youjie Li
Summary: Leukemia cells induce immunosuppression of the bone marrow microenvironment, preventing the immune system from clearing tumor cells. The PD-1/PD-L1 axis acts as a significant mechanism for tumor cells to evade immune surveillance. The development of drugs targeting PD-1/PD-L1 in leukemia is still at the clinical-trial stage.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Fang Wang, Liqiong Yang, Mintao Xiao, Zhuo Zhang, Jing Shen, Songyot Anuchapreeda, Singkome Tima, Sawitree Chiampanichayakul, Zhangang Xiao
Summary: Anti-PD-1/PD-L1 immunotherapy has been proven effective in cancer treatment. This study found that PD-L1 was elevated in AML patients and high expression of PD-L1 was associated with poor overall survival rate. The ECM-receptor interaction and PI3K-AKT signaling pathway were identified as important downstream pathways of PD-L1. Knockdown of PD-L1 inhibited AML cell proliferation and induced cell apoptosis.
SCIENTIFIC REPORTS
(2022)
Review
Hematology
Jan Philipp Bewersdorf, Rory M. Shallis, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have shown mixed results in clinical trials in patients with acute myeloid leukemia and myelodysplastic syndromes, but there is optimism for the future of this field. Advances in understanding the immunologic landscape, potential biomarkers, and resistance mechanisms provide hope, but challenges such as the lack of validated biomarkers and the development of safe combination therapies still need to be addressed.
Article
Immunology
Maria-Luisa Del Rio, Jose-Antonio Perez-Simon, Jose-Ignacio Rodriguez-Barbosa
Summary: The expression of PD-L1 on A20 leukemia tumor cells modulates the interaction between CD8 T cells and tumor-specific antigens, but does not inhibit NK cell-mediated hybrid resistance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ana Bocanegra, Gonzalo Fernandez-Hinojal, Daniel Ajona, Ester Blanco, Miren Zuazo, Maider Garnica, Luisa Chocarro, Elvira Alfaro-Arnedo, Sergio Pineiro-Hermida, Pilar Morente, Leticia Fernandez, Ana Remirez, Miriam Echaide, Maite Martinez-Aguillo, Idoia Morilla, Beatriz Tavira, Alejandra Roncero, Carolina Gotera, Alfonso Ventura, Nerea Recalde, Jose G. Pichel, Juan Jose Lasarte, Luis Montuenga, Ruth Vera, Ruben Pio, David Escors, Grazyna Kochan
Summary: Recent studies show that baseline functional immunity is crucial for the success of immune checkpoint blockade therapies. In this study, high-dimensional systemic immune profiling was performed on non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders had a higher diversity of myeloid phenotypes in their peripheral blood. A diversity index was defined as a potential biomarker of response. Fractalkine (FKN), a chemokine linked to immune chemotaxis and adhesion, was identified as a biomarker of response and correlated with myeloid cell diversity. FKN inhibited lung adenocarcinoma growth in both human and mouse models through the involvement of systemic effector NK cells and increased tumor immune infiltration. FKN also sensitized mouse lung cancer models resistant to anti-PD-1 treatment to immunotherapy, indicating its potential therapeutic use in combination with immunotherapy.
Article
Oncology
Yang Ruan, Longlong Xie, Aijun Zou
Summary: This study analyzed the genetic and clinical features of children with CDKN2A/B mutations in acute lymphoblastic leukemia (ALL) and evaluated the expression and significance of PD-1 and PD-L1 in serum. The study found that CDKN2A rs3088440 and CDKN2B rs2069426 may be related to the occurrence and development of ALL in Chinese children. Additionally, PD-1/PD-L1 may be involved in the immune escape process of ALL, which could be a novel target for treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Immunology
Mohammad Jalili-Nik, Arash Soltani, Baratali Mashkani, Houshang Rafatpanah, Seyed Isaac Hashemy
Summary: Immunotherapy through immune checkpoints blockade has revolutionized the treatment of solid tumors. Blockade of PD-1 and its ligand has shown promising results in clinical studies, with ongoing investigations into the potential therapeutic effects of PD-1 inhibition in ATLL patients.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Article
Cell Biology
Min Liu, Feng Wei, Jian Wang, Wenwen Yu, Meng Shen, Ting Liu, Dong Zhang, Yang Wang, Xiubao Ren, Qian Sun
Summary: MDSCs activate the PI3K/AKT/NF-kappa B pathway in B cells via the PD-1/PD-L1 axis, regulating the immunosuppressive function of Bregs. Inhibition of PD-1/PD-L1 or PI3K/AKT signaling suppresses tumor growth and the immunosuppressive functions of Bregs. Dual suppression of PD-1/PD-L1 and PI3K/AKT shows better antitumor effect.
CELL DEATH & DISEASE
(2021)
Article
Cardiac & Cardiovascular Systems
Katharina Lechner, Johannes Scherr, Elke Lorenz, Benjamin Lechner, Bernhard Haller, Alexander Krannich, Martin Halle, Rolf Wachter, Andre Duvinage, Frank Edelmann
Summary: This study evaluated the associations of omega-3 fatty acid blood levels with cardiac function, functional capacity, and cardiometabolic risk markers in patients with heart failure with preserved ejection fraction (HFpEF). Higher omega-3 index was found to be associated with a more favorable cardiometabolic risk profile, predicting higher aerobic capacity and lower BMI/truncal adiposity in HFpEF patients.
CLINICAL RESEARCH IN CARDIOLOGY
(2022)
Article
Medicine, General & Internal
Quirin Bachmann, Flora Haberfellner, Maike Buettner-Herold, Carlos Torrez, Bernhard Haller, Volker Assfalg, Lutz Renders, Kerstin Amann, Uwe Heemann, Christoph Schmaderer, Stephan Kemmner
Summary: The increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. There is a need for better decision guidance and more accurate tools to assess organ quality.
FRONTIERS IN MEDICINE
(2022)
Article
Education & Educational Research
Hannah P. K. Rubisch, Anna-Lena Blaschke, Pascal O. Berberat, Cornelia S. Fuetterer, Bernhard Haller, Martin Gartmeier
Summary: We analysed interactions between teachers and students during video-recorded bedside teaching sessions in internal medicine, orthopaedics and neurology. Our research focused on the types of student mistakes, clinical teachers' reactions to them and if they use different strategies to address different types of mistakes. The most common student mistakes were reproduction mistakes, which were associated with the highest level of rejection and the lowest level of elaboration. Students were allowed more time to correct mistakes in the areas of analysis or application of skills and knowledge. There was a decrease in the rate of making mistakes for neurology and orthopaedics compared to internal medicine.
ADVANCES IN HEALTH SCIENCES EDUCATION
(2023)
Article
Computer Science, Interdisciplinary Applications
Alexander Hapfelmeier, Roman Hornung, Bernhard Haller
Summary: Hypothesis testing of variable importance measures (VIMPs) is an ongoing research topic. Different approaches have been proposed to address the computational costs associated with these tests, including heuristic approaches, formal tests, and non-parametric permutation tests. The use of sequential permutation tests and sequential p-value estimation can significantly reduce the computational costs of conventional permutation tests. Simulation studies and application studies confirm the theoretical properties and numerical stability of these methods.
COMPUTATIONAL STATISTICS & DATA ANALYSIS
(2023)
Article
Physiology
Julia Schoenfeld, Astrid Roeh, Stefan Holdenrieder, Pia von Korn, Bernhard Haller, Kimberly Krueger, Peter Falkai, Martin Halle, Alkomiet Hasan, Johannes Scherr
Summary: This study investigated the impact of prolonged and strenuous exercise on markers of immunogenic cell damage. The findings revealed that HMGB1, sRAGE, nucleosomes, hs-TnT, and hs-CRP significantly increased immediately after the race and returned to baseline within 24-72 hours.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Immunology
Renate Ilona Hausinger, Quirin Bachmann, Timotius Crone-Rawe, Nora Hannane, Ina Monsef, Bernhard Haller, Uwe Heemann, Nicole Skoetz, Nina Kreuzberger, Christoph Schmaderer
Summary: Additional SARS-CoV-2 vaccine doses are effective and safe in improving the immune response and preventing severe disease for kidney transplant recipients (KTRs). Studies show that after three or four vaccine doses, the rate of de novo seroconversion ranged from 32% to 60% and 25% to 37% respectively. Variant-specific neutralization was 59% to 70% for Delta and 12% to 52% for Omicron. Severe disease after infection was rare, but KTRs lacked immune responses after vaccination. Higher rates of severe disease were found in KTRs compared to the general population.
Article
Health Care Sciences & Services
Christopher Holzmann-Littig, David Stadler, Maria Popp, Peter Kranke, Falk Fichtner, Christoph Schmaderer, Lutz Renders, Matthias Christoph Braunisch, Tarek Assali, Louise Platen, Marjo Wijnen-Meijer, Julia Luehnen, Anke Steckelberg, Lisa Pfadenhauer, Bernhard Haller, Cornelia Fuetterer, Christian Seeber, Christian Schaaf
Summary: The study investigated the information-seeking behavior of different healthcare worker groups in Germany. The findings revealed that non-physician HCWs were more likely to rely on public information sources, highlighting the need for employers/institutions to provide targeted COVID-19 information for different HCW groups.
Article
Clinical Neurology
Andreas Wolfgang Wolff, Bernhard Haller, Antonia Franziska Demleitner, Dominik Puerner, Johanna Niederschweiberer, Isabell Cordts, Erica Westenberg, Paul Lingor
Summary: This study aims to assess the long-term impact of the COVID-19 pandemic on patients with Parkinson's disease (PwP) and their relatives in Germany. The study found that despite some resumption of social and group activities, healthcare services remained disrupted. PwP reported worsened symptoms, resulting in new symptoms and increased burden for their relatives. Younger patients and those with longer disease duration were identified as particularly at risk.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Obstetrics & Gynecology
Johanna Knoke, Roxana Raab, Kristina Geyer, Monika Spies, Bernhard Haller, Hans Hauner
Summary: Antibiotic therapies during pregnancy and breastfeeding pose challenges, and the frequency of antibiotic use is not well-known in Germany. The GeliS study reveals that approximately one in five women receive at least one antibiotic treatment during this phase.
GEBURTSHILFE UND FRAUENHEILKUNDE
(2023)
Article
Engineering, Biomedical
Nikolas Forstl, Franz Sueb, Carsten Englert, Sebastian Dendorfer
Summary: This study developed a temporary reverse shoulder implant prototype that allows intraoperative measurement of shoulder stiffness. The stability of the shoulder can be assessed using joint angle and torque measurement techniques. The proposed design provides a method for intraoperative assessment of shoulder stiffness.
MEDICAL ENGINEERING & PHYSICS
(2023)
Article
Oncology
Felix Johnson, Benedikt Hofauer, Markus Wirth, Barbara Wollenberg, Fabian Stoegbauer, Susan Notohamiprodjo, Bernhard Haller, Robin Reschke, Andreas Knopf, Ulrich Strassen
Summary: In this study, it was found that pleomorphic adenoma in salivary glands has a high concentration of the somatostatin receptor 2 (SSTR2), which may allow for non-invasive diagnosis and treatment of this tumor. Reliable preoperative diagnosis of salivary gland tumors is difficult. Immunohistochemistry testing showed that 42.3% of pleomorphic adenoma tumors demonstrated positive expression of SSTR2.
Article
Gastroenterology & Hepatology
Joerg D. Ulrich, Paul Rechberger, Jeannine Bachmann, Alexander Herner, Guido V. Figura, Tobias Lahmer, Veit Phillip, Ulrich Mayr, Bernhard Haller, Moritz Jesinghaus, Roland M. Schmid, Mohamed Abdelhafez, Christoph Schlag
Summary: This study evaluated the efficacy and safety of cold snare polypectomy (CSP) for polyps sized between 10 and 15 mm. Results showed that CSP was efficient and safe for removing colorectal polyps of this size. If CSP failed in larger polyps, immediate conversion to hot snare polypectomy (HSP) was successful for resection.
Article
Mathematical & Computational Biology
Hannah Schuster, Bernhard Haller, Sengul Sancak, Johanna Erber, Roland M. Schmid, Tobias Lahmer, Sebastian Rasch
Summary: The purpose of this study is to evaluate the efficacy of the currently implemented correction function and improve it further. The results show that the new correction formula has better performance in reducing bias, improving correlation, and reliability compared to the currently implemented formula.
MATHEMATICAL BIOSCIENCES AND ENGINEERING
(2023)
Article
Sport Sciences
Melanie Heitkamp, Bianca Spanier, Pia von Korn, Sebastian Knapp, Claudia Gross, Bernhard Haller, Martin Halle
Summary: The F-PROTECT study aimed to evaluate the feasibility of introducing a high volume and long duration of physical activity in colorectal cancer patients. The results showed that although 50 patients were recruited, the training attendance rate was only 64%. Therefore, strategies specifically designed for this patient group need to be developed and investigated to improve long-term physical activity.
TRANSLATIONAL SPORTS MEDICINE
(2023)
Article
Medicine, Research & Experimental
Christian Klenk, Johanna Erber, David Fresacher, Stefan Roehrl, Manuel Lengl, Dominik Heim, Hedwig Irl, Martin Schlegel, Bernhard Haller, Tobias Lahmer, Klaus Diepold, Sebastian Rasch, Oliver Hayden
Summary: The study presents a point-of-care compatible method for quantitatively analyzing blood cell aggregates in COVID-19 patients. The severity of COVID-19 is found to be significantly associated with the amount of platelet and platelet-leukocyte aggregates. The study highlights the potential of the method in supporting risk stratification and preventing complications in severe COVID-19 patients and other medical disorders involving immune cell aggregation.
COMMUNICATIONS MEDICINE
(2023)