Article
Oncology
Kang Li, Jun Liu, Lin Wu, Yajie Xiao, Jia Li, Haijian Du, Zhikun Zhao, Chao Sun, Yongtian Zhao, Jie Yang, Dongfang Wu, Zhuxiang Zhao, Bolin Chen
Summary: High tumor mutation burden was significantly associated with high PD-L1 expression in Chinese lung adenocarcinoma patients, with specific gene alterations found in the high PD-L1 expression group. Pathway analysis revealed significant differences among different expression groups.
CANCER CELL INTERNATIONAL
(2022)
Article
Cell Biology
Yuan Wang, Zhenchang Jia, Chenxi Liang, Yunfei He, Min Cong, Qiuyao Wu, Pu Tian, Dasa He, Xiang Miao, Beibei Sun, Yue Yin, Chao Peng, Feng Yao, Da Fu, Yajun Liang, Peiyuan Zhang, Hua Xiong, Guohong Hu
Summary: The downregulation of MTSS1 leads to upregulation of PD-L1 in lung adenocarcinoma, impairing CD8(+) lymphocyte function and promoting tumor progression. MTSS1 downregulation correlates with improved efficacy of ICB treatment. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 to monoubiquitinate PD-L1 at Lysine 263, resulting in PD-L1 endocytic sorting and lysosomal degradation. Additionally, EGFR-KRAS signaling suppresses MTSS1 and upregulates PD-L1 in lung adenocarcinoma. Furthermore, combining AIP4-targeting with the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in both immunocompetent and humanized mouse models.
Article
Biochemistry & Molecular Biology
Eiko Sakurai, Hisato Ishizawa, Yuka Kiriyama, Ayano Michiba, Yasushi Hoshikawa, Tetsuya Tsukamoto
Summary: This study investigates the relationship between gamma H2AX and PD-L1 expression in lung cancer. Positive correlation between gamma H2AX and PD-L1, especially in lung adenocarcinoma, is observed, suggesting that gamma H2AX could serve as an alternative marker for PD-L1 and tumor mutation burden (TMB).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hay-Ran Jang, Sol-Bi Shin, Chang-Hyeon Kim, Jae-Yeon Won, Rong Xu, Da-Eun Kim, Hyungshin Yim
Summary: The phosphorylation of vimentin by PLK1 activates TGF-beta signaling pathway in lung adenocarcinoma, leading to metastasis and immune escape through PD-L1 expression. Clinical relevance studies revealed an inverse correlation between the expressions of VIM, PLK1, and CD274 and the survival rates of patients with primary and metastatic lung adenocarcinoma.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Oncology
Xiaoling Xu, Na Li, Ding Wang, Wei Chen, Yun Fan
Summary: This study suggests that patients with invasive mucinous adenocarcinoma (IMA) of the lung exhibit down-regulated PD-L1 expression and less CD8+ TIL infiltration in the tumor microenvironment, along with a lower frequency of EGFR mutations and a higher rate of ALK rearrangements compared to non-IMA patients. Furthermore, CD8+ TIL infiltration serves as an independent prognostic factor for poor outcomes in IMA patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Young Wha Koh, Bumhee Park, Se Hee Jung, Jae-Ho Han, Seokjin Haam, Hyun Woo Lee
Summary: We investigated the distribution of immune cell types and the response to PD-1/PD-L1 inhibitors according to EGFR mutation profile in lung adenocarcinoma. The results showed that EGFR wild-type carcinomas had higher numbers of certain immune cells compared to EGFR mutant carcinomas, and EGFR rare variants were predicted to have a better response to PD-1/PD-L1 inhibitors. Therefore, EGFR rare mutation form could be a potential target for PD-1/PD-L1 inhibitor therapy in lung adenocarcinoma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Xuan Zhao, Yulin Bao, Bi Meng, Zijian Xu, Sijin Li, Xu Wang, Rui Hou, Wen Ma, Dan Liu, Junnian Zheng, Ming Shi
Summary: Developing biomarkers for predicting the efficacy of immune checkpoint inhibitor therapies is important for avoiding side effects and economic burden. Current assays evaluating PD-L1 expression are imperfect, but recent studies are advancing the methodologies to improve accuracy. This includes standardization of immunohistochemistry tests and the use of novel in vivo probes and liquid biopsy. Considering PD-L1 expression on non-tumor cells and utilizing artificial intelligence can further enhance the predictive accuracy of PD-L1 as a biomarker.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Mao Lin, Zongyao Huang, Yingfu Chen, Hongtao Xiao, Ting Wang
Summary: This review systematically summarizes the outcomes of lung cancer patients with chronic obstructive pulmonary disease (COPD) after anti-PD-1/PD-L1 treatment and discusses the role of COPD in regulating the tumor immune microenvironment (TIME) in lung cancer immunotherapy, providing novel insights for the clinical treatment of lung cancer patients with COPD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Loick Galland, Anne Laure Le Page, Julie Lecuelle, Frederic Bibeau, Youssef Oulkhouir, Valentin Derangere, Caroline Truntzer, Francois Ghiringhelli
Summary: The study aimed to identify biomarkers for the efficacy of ICI treatment in non-squamous NSCLC, finding that TTF1 expression and PD-L1 status can predict PFS and OS, improving prognosis prediction accuracy.
Article
Cell Biology
Congkuan Song, Zhiquan Wu, Qingwen Wang, Yujin Wang, Zixin Guo, Sheng Li, Weidong Hu
Summary: A study identified two genes that can predict response to immunotherapy in lung adenocarcinoma patients, developed a signature to distinguish high- and low-risk patients, and constructed a nomogram by combining immune prognostic signature with clinical features.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Wenhua Xu, Jiajun Cui, Linqing Wu, Caigu He, Gang Chen
Summary: Chronic exposure to arsenic negatively affects T cell anti-tumor immunity, promoting lung cancer development. The up-regulation of PD-1/PD-L1 and increase in Tregs, along with decreased CD8/Treg ratio, hinder T cell anti-tumor function in the lungs, enhancing lung tumorigenesis. Inhibition of PD-1/PD-L1 shows potential as a preventive strategy to mitigate the tumorigenic effects of chronic arsenic exposure.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Nitin Roper, Moises J. Velez, Alberto Chiappori, Yoo Sun Kim, Jun S. Wei, Sivasish Sindiri, Nobuyuki Takahashi, Deborah Mulford, Suresh Kumar, Kris Ylaya, Christopher Trindade, Irena Manukyan, Anna-Leigh Brown, Jane B. Trepel, Jung-Min Lee, Stephen Hewitt, Javed Khan, Anish Thomas
Summary: This study identifies elevated Notch signaling as a significant predictor of clinical benefit in immune checkpoint blockade (ICB) for relapsed small cell lung cancer (SCLC) patients. Activation of Notch signaling induces a low NE phenotype, leading to increased expression of antigen processing and presentation machinery (APM) genes and improved intrinsic tumor immunity.
NATURE COMMUNICATIONS
(2021)
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
Oncology
Kei Kunimasa, Yosuke Hirotsu, Kenji Amemiya, Keiichiro Honma, Harumi Nakamura, Kazumi Nishino, Masao Omata
Summary: In this study, the association between PD-L1 expression in tumor cells and underlying genetic mutations was investigated using laser microdissection and next-generation sequencing analysis. The analysis showed no association between PD-L1 expression heterogeneity and genetic variants, but revealed a correlation between PD-L1 expression and the number of tumor infiltrating lymphocytes.
Article
Oncology
Fabien Forest, Francois Casteillo, Vanessa Da Cruz, Violaine Yvorel, Tiphanie Picot, Francois Vassal, Olivier Tiffet, Michel Peoc'h
Summary: This study found that metastases of lung adenocarcinoma exhibit various histopathological patterns, each with different levels of PD-L1 expression. Additionally, the heterogeneity in PD-L1 expression among different patterns is closely related.
Article
Biochemical Research Methods
Gabor Toth, Domonkos Pal, Simon Sugar, Ilona Kovalszky, Katalin Dezso, Gitta Schlosser, Laszlo Drahos, Lilla Turiak
Summary: This study investigated the content and sulfation pattern of chondroitin sulfate (CS) and heparan sulfate (HS) in human hepatocellular carcinoma and cirrhotic liver tissues, considering the etiology of the diseases. Major differences were observed in the total abundance and sulfation pattern of CS and HS chains, providing important insights into the molecular mechanisms of chronic liver diseases.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Anna Kerpel-Fronius, Zsuzsanna Monostori, Gabor Kovacs, Gyula Ostoros, Istvan Horvath, Diana Solymosi, Orsolya Pipek, Ferenc Szatmari, Anita Kovacs, Zsolt Markoczy, Livia Rojko, Ferenc Renyi-Vamos, Konrad Hoetzenecker, Krisztina Bogos, Zsolt Megyesfalvi, Balazs Dome
Summary: Lung cancer is the leading cause of cancer-related deaths in Hungary, highlighting the need for a national screening program. The HUNCHEST pilot program found that LDCT screening may facilitate early diagnosis and curative treatment.
EUROPEAN RADIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Orsolya Oravecz, Andrea Balogh, Roberto Romero, Yi Xu, Kata Juhasz, Zsolt Gelencser, Zhonghui Xu, Gaurav Bhatti, Roger Pique-Regi, Balint Peterfia, Petronella Hupuczi, Ilona Kovalszky, Padma Murthi, Adi L. Tarca, Zoltan Papp, Janos Matko, Nandor Gabor Than
Summary: Proteoglycan macromolecules, specifically syndecan-1, play crucial roles in various physiological processes during placenta development and healthy pregnancy. Dysregulated expression of proteoglycans, including syndecan-1, has been observed in pregnancy complications such as pre-eclampsia and fetal growth restriction. Further research is needed to explore the potential diagnostic and therapeutic applications of proteoglycans in complicated pregnancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Orsolya Anna Pipek, Istvan Csabai
Summary: Epigenetic changes have been extensively studied in relation to the aging process in humans. DNA methylation has been used as a surrogate measure of biological age, and various epigenetic clocks have been designed to predict age based on different tissues and methylation platforms. In this study, researchers aimed to improve the accuracy of one of the most commonly used epigenetic age predictors, the Horvath pan-tissue epigenetic clock, using data from the latest Illumina methylation platform. The updated epigenetic clocks showed superior performance compared to the original model on a test set of samples, especially on EPIC array data. This updated model can predict chronological age with great precision in multiple tissue types and data platforms.
JOURNAL OF MATHEMATICAL CHEMISTRY
(2023)
Article
Oncology
David Dora, Christopher Rivard, Hui Yu, Shivaun Lueke Pickard, Viktoria Laszlo, Tunde Harko, Zsolt Megyesfalvi, Csongor Gerdan, Elek Dinya, Konrad Hoetzenecker, Fred R. Hirsch, Zoltan Lohinai, Balazs Dome
Summary: This study characterizes the microenvironment of SCLC and identifies potential therapeutic targets by analyzing the expression patterns of SCLC subtype markers and immune checkpoints. The results show that STING and MHCII are expressed in SCLC, and increased immune infiltration and STING expression are associated with better prognosis. These findings suggest that STING may be a promising therapeutic target for limited-stage SCLC.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
David Dora, Syeda Mahak Zahra Bokhari, Kenan Aloss, Peter Takacs, Juliane Zsuzsanna Desnoix, Gyorgy Szklenarik, Patrick Deniz Hurley, Zoltan Lohinai
Summary: Immune checkpoint inhibitors have revolutionized tumor management, but they can also lead to immune-related adverse effects (irAEs). Recent research has found a link between irAEs and the gut microbiome, suggesting that specific microbial patterns and metabolites might be associated with the severity of toxicity symptoms. Identifying these biological factors could help predict and manage irAEs more effectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alexandra Kalmar, Orsolya Galamb, Gitta Szabo, Orsolya Pipek, Anna Medgyes-Horvath, Barbara K. Bartak, Zsofia B. Nagy, Krisztina A. Szigeti, Sara Zsigrai, Istvan Csabai, Peter Igaz, Bela Molnar, Istvan Takacs
Summary: By analyzing tissue biopsies and plasma-derived cfDNA samples, we found that liquid biopsy using whole-exome sequencing and targeted sequencing is a suitable and potentially preferred method for genetic characterization of colorectal cancer patients in the future.
Article
Oncology
David Dora, Imre Voros, Zoltan V. Varga, Peter Takacs, Vanda Teglasi, Judit Moldvay, Zoltan Lohinai
Summary: The expression of BRAF RNA in lung adenocarcinoma is increased and associated with tumor necrosis, immune checkpoint biology, and outcomes. Further research on targeting the overexpressed BRAF pathway in lung adenocarcinoma is recommended.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
Article
Oncology
David Dora, Balazs Ligeti, Tamas Kovacs, Peter Revisnyei, Gabriella Galffy, Edit Dulka, Daniel Krizsan, Regina Kalcsevszki, Zsolt Megyesfalvi, Balazs Dome, Glen J. Weiss, Zoltan Lohinai
Summary: Our study identified specific gut microbiome features that may be indicative of the efficacy of anti-PD1 immunotherapy and PD-L1 expression in non-small cell lung cancer patients. The key bacteria associated with progression-free survival were confirmed through statistical modeling and validation on an additional patient cohort. Additionally, taxonomic profiles and metabolic pathways were found to be predictive of efficacy and PD-L1 expression, respectively.
Article
Oncology
Orsolya Pipek, Laura Vizkeleti, Viktoria Doma, Donat Alpar, Csaba Bödör, Sarolta Karpati, Jozsef Timar
Summary: Malignant melanoma of the skin, primarily on UV-exposed skin, is commonly associated with mutant BRAF, RAS, and KIT oncogenes. The genetic makeup of triple-wild-type melanoma (BRAF, NRAS, and NF1) has been studied before, but with mixed rare and common histopathological subtypes. In this study, whole genome sequencing was used to characterize triple-wild-type melanoma, excluding rare histopathological subtypes. Unrecognized drivers were identified among passenger mutations in some cases.
Article
Oncology
Sebastian Blaj, David Dora, Zoltan Lohinai, Zoltan Herold, Attila Marcell Szasz, Jonas Herzberg, Roland Kodacsi, Saher Baransi, Hans Juergen Schlitt, Matthias Hornung, Jens M. Werner, Przemyslaw Slowik, Miklos Acs, Pompiliu Piso
Summary: The prognosis of patients with pseudomyxoma peritonei (PMP) has improved due to better understanding of the disease and the introduction of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Reliable prognostic factors include peritoneal cancer index, extent of cytoreduction, and tumor markers. This study confirms the importance of these factors in a large cohort of PMP and low-grade histology patients.
Article
Biology
Gabor Szegvari, David Dora, Zoltan Lohinai
Summary: Understanding the effects of the tumor microenvironment is crucial for advancing cancer treatments. In vitro and in vivo studies are challenging to reproduce, but in silico methods, such as network models, can help overcome these barriers. We focused on macrophages and their environment to study their polarization and built a Boolean control network model to simulate combinatorial treatment options for influencing macrophage polarization.
Article
Oncology
David Dora, Glen J. Weiss, Zsolt Megyesfalvi, Gabriella Gallfy, Edit Dulka, Anna Kerpel-Fronius, Judit Berta, Judit Moldvay, Balazs Dome, Zoltan Lohinai
Summary: This study investigates the role of the human gut microbiome in predicting the response to immunotherapy in NSCLC patients. By integrating shotgun metagenomics and quantitative texture analysis of CT images, the study identifies microbiome signatures associated with therapeutic response and survival. The findings suggest that a combination of these variables could be used to create a predictive model for treatment outcomes.
Article
Cell Biology
Alexander Ries, Astrid Slany, Christine Pirker, Johanna C. C. Mader, Doris Mejri, Thomas Mohr, Karin Schelch, Daniela Flehberger, Nadine Maach, Muhammad Hashim, Mir Alireza Hoda, Balazs Dome, Georg Krupitza, Walter Berger, Christopher Gerner, Klaus Holzmann, Michael Grusch
Summary: In this study, novel hTERT-transduced mesothelial cell and Meso-CAF models were generated and characterized, and their impact on PM cell growth was investigated.