Review
Immunology
Hui Zhang, Qi-Wei Li, Yuan-Yuan Li, Xue Tang, Ling Gu, Han-Min Liu
Summary: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance and pressure, and the relationship between myeloid-derived suppressor cells (MDSCs) and PH has been studied. MDSCs are a group of cells that can suppress T-cell responses and potentially exacerbate the development of diseases. Understanding the relationship between MDSCs and PH can help identify potential therapeutic targets for the treatment of PH.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Virginia Camacho, Valeriya Kuznetsova, Robert S. Welner
Summary: The immune microenvironment plays a crucial role in regulating hematopoiesis and immune cell dysfunction significantly contributes to neoplastic disease. Leukemic inflammatory cytokines can alter immune cells, and targeting the immune landscape may have therapeutic value in limiting leukemia growth. Further research is needed to understand how leukemic cytokines impact immune cells and potential immunotherapeutic approaches for patients with hematological myeloid malignancies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Iosif Papafragkos, Efrosyni Markaki, Christina Kalpadakis, Panayotis Verginis
Summary: Myeloid-derived suppressor cells (MDSCs) are potent regulators of the immune system, playing a role in cancer but their specific contribution to lymphomas remains unclear. This review focuses on MDSCs in lymphomas, discussing literature and lessons learned from animal models, and highlights future research directions and challenges in understanding the immune system complexities in malignancies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ching-Chuan Hsieh, Cheng-Chih Chang, Yung-Chien Hsu, Chun-Liang Lin
Summary: In the development of diabetic kidney disease, the dysregulation of glomerular cell types is crucial, and MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ru Li, Mousumi Beto Mukherjee, Jun Lin
Summary: In this review, the effects of cytokines and chemokines on myeloid-derived suppressor cells in cancer metastasis are summarized. Cytokines and chemokines in the tumor microenvironment alter the functional properties of MDSCs and are involved in their production, infiltration, and immunosuppressive functions. The manipulation of MDSCs by tumors through cytokine and chemokine signaling is discussed, as well as potential treatment strategies targeting these signaling pathways to combat the immunosuppressive activities of MDSCs and improve disease outcomes.
Article
Biochemistry & Molecular Biology
Man Liu, Hongxia Zhang, Lu Zhang, Xin Liu, Simin Zhou, Xiaoyi Wang, Weilong Zhong, Jie Zhang, Bangmao Wang, Jingwen Zhao, Lu Zhou
Summary: The study found that increased expression and activation of RIP3 in livers of autoimmune hepatitis patients and animal models, and inhibition of RIP3 kinase prevented immune-mediated hepatitis by promoting MDSCs infiltration with immunoregulatory properties. This indicates that RIP3 blockade may be a novel avenue for autoimmune hepatitis treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Rheumatology
Jiram Torres-Ruiz, Abdiel Absalon-Aguilar, Juan Alberto Reyes-Islas, Fabiola Cassiano-Quezada, Nancy R. Mejia-Dominguez, Alfredo Perez-Fragoso, Jose Luis Maravillas-Montero, Carlos Nunez-Alvarez, Guillermo Juarez-Vega, Alejandro Culebro-Bermejo, Diana Gomez-Martin
Summary: In patients with idiopathic inflammatory myopathies (IIMs), the proportion of myeloid-derived suppressor cells (MDSCs) is increased. These MDSCs express higher levels of PD-L1 and arginase-1 and are correlated with disease activity, damage accrual, and serum cytokines.
Article
Oncology
Ran Li, Xiaolu Wu, Kai Xue, Junmin Li
Summary: ITGAL is highly expressed in acute myeloid leukemia and is associated with poor prognosis. It is correlated with age and cytogenetic risk classifications, but not with AML driver gene mutations. Functional analysis reveals that ITGAL is involved in the production and metabolic process of cytokines. Additionally, ITGAL is closely related to the number of MDSCs and cytokine production.
CANCER CELL INTERNATIONAL
(2022)
Article
Oncology
Yu Chen, Yanquan Xu, Huakan Zhao, Yu Zhou, Jiangang Zhang, Juan Lei, Lei Wu, Mingyue Zhou, Jingchun Wang, Shuai Yang, Xiao Zhang, Guifang Yan, Yongsheng Li
Summary: Cancer immunotherapy targeting myeloid-derived suppressor cells (MDSCs) is a promising anti-cancer strategy. This study explored the regulatory mechanisms of cholesterol metabolic reprogramming in MDSCs and found that cholesterol deficiency increased the immunosuppressive activity of MDSCs. Mechanistically, cholesterol elimination induced nuclear accumulation of LXR beta and enhanced the binding of LXR beta-RXR alpha on Arg1 promoter. Furthermore, itraconazole improved MDSC immunosuppressive activity and promoted tumor growth by inhibiting the RIPK3-AKT-mTORC1 pathway and impeding cholesterol synthesis.
Review
Immunology
Maria Luisa Sanchez-Leon, Carlos Jimenez-Cortegana, Gabriel Cabrera, Elba Monica Vermeulen, Luis de la Cruz-Merino, Victor Sanchez-Margalet
Summary: Dendritic cells (DCs) play a diminished role in various malignancies due to immunosuppressive conditions in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs) accumulate in the TME and inhibit DC functions, maturation, and development. DC-based vaccines have been developed to improve antitumor immunity, and their effectiveness in murine models and cancer patients, alone or in combination with other treatments, has been explored.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Nancy D. Ebelt, Edwin R. Manuel
Summary: Cancer cells can escape surveillance through epigenetic modifications, while hypomethylating agents (HMAs) have shown promise as a milder treatment option for leukemia patients. In this study, HMAs were tested on murine leukemias and found to re-establish immune-related gene expression, reduce leukemic burden, and improve survival. However, resistance and immune checkpoint protein expression were observed.
Review
Immunology
Rong Fan, Nathan De Beule, Anke Maes, Elke De Bruyne, Eline Menu, Karin Vanderkerken, Ken Maes, Karine Breckpot, Kim De Veirman
Summary: MDSC play a key role in the immunosuppressive microenvironment of hematological cancers, associated with tumor cell survival and drug resistance. Despite intensive studies on the phenotype, function, and prognostic value of MDSC in hematological cancers, therapeutic targeting of this cell population remains challenging.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Mary M. Stevenson, Rajesh M. Valanparambil, Mifong Tam
Summary: The article suggests that immune suppression caused by helminth infections may be related to myeloid-derived suppressor cells (MDSC), and the data collected so far support this hypothesis. Future strategies targeting MDSC could enhance immune responses to eliminate adult worms and prevent reinfection.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Kristin C. Hicks, Yulia Y. Tyurina, Valerian E. Kagan, Dmitry I. Gabrilovich
Summary: Immunosuppressive myeloid cells generate oxidized lipids, which play a role in immune suppression in cancer.
Review
Immunology
Yang Zhao, Junfeng Du, Xiaofei Shen
Summary: Myeloid-derived suppressor cells (MDSCs) are a major negative regulator in tumor microenvironment (TME) by inhibiting immune response and promoting immunosuppression. This review focuses on the features of MDSCs in TME and potential targets for tumor immunotherapy. Therapies aiming to reprogram TME, prevent MDSC immunosuppression, promote MDSC differentiation, and impact MDSC recruitment and abundance in tumor site are discussed. Combinatorial strategies to improve clinical efficacy and outcomes of cancer patients through better understanding of MDSCs generation and suppression in TME are also summarized.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Anuhar Chaturvedi, Charu Gupta, Razif Gabdoulline, Nora M. Borchert, Ramya Goparaju, Stefan Kaulfuss, Kerstin Goerlich, Renate Schottmann, Basem Othman, Julia Welzenbach, Olaf Panknin, Markus Wagner, Robert Geffers, Arnold Ganser, Felicitas Thol, Andrea Haegebarth, Michael Jeffers, Michael Heuser
Summary: The study demonstrates that the combination treatment of mIDH1 inhibitors and azacitidine has significant efficacy in AML patients, reducing leukemia stem cell numbers through different mechanisms and signaling pathways. The strong synergy between the two treatments is mediated through inhibition of MAPK/ERK and Rb/E2F signaling, suggesting an improved outcome for IDH1 mutated AML patients.
Article
Pharmacology & Pharmacy
Ana Ruiz-Garcia, Naveed Shaik, Swan Lin, Catriona Jamieson, Michael Heuser, Geoffrey Chan
Summary: The study explored the relationship between Glasdegib exposure and adverse events, finding a significant correlation with dysgeusia, muscle spasms, renal toxicity, and QT interval prolonged. The survival benefit was not exposure-dependent, and the probability of developing AEs for safety endpoints was low, hence no starting dose adjustments for Glasdegib are recommended based on the observed safety profile.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Hematology
Hanna Kirchhoff, Uemran Karsli, Caroline Schoenherr, Karin Battmer, Sergej Erschow, Steven R. Talbot, Doris Steinemann, Michael Heuser, Olaf Heidenreich, Denise Hilfiker-Kleiner, Arnold Ganser, Matthias Eder, Michaela Scherr
Summary: The study analyzed how Venetoclax and Inotuzumab Ozogamicin induce apoptosis in BCP-ALL patients, and found that the combined use of Venetoclax, dexamethasone, and Inotuzumab Ozogamicin can have a synergistic effect, providing possibilities for improving patient prognosis.
Article
Oncology
Daria Warnstorf, Randa Bawadi, Andrea Schienke, Renate Strasser, Gunnar Schmidt, Thomas Illig, Marcel Tauscher, Felicitas Thol, Michael Heuser, Doris Steinemann, Claudia Davenport, Brigitte Schlegelberger, Yvonne Lisa Behrens, Gudrun Goehring
Summary: The study showed that the unbalanced translocation der(5;17) in MDS/AML is associated with biallelic inactivation of TP53, often accompanied by loss of genetic material in chromosomes 5q and 17p.
GENES CHROMOSOMES & CANCER
(2021)
Article
Chemistry, Medicinal
Sahil Arora, Gaurav Joshi, Anuhar Chaturvedi, Michael Heuser, Santoshkumar Patil, Raj Kumar
Summary: The allosteric regulation of pyruvate kinase M2 (PKM2) plays a significant role in cellular activity and has potential applications in treating metabolic dysfunction and related conditions. This perspective article focuses on medicinal chemistry strategies for designing PKM2 inhibitors and activators with improved efficacy and selectivity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Correction
Oncology
Arnold Kloos, Konstantinos Mintzas, Lina Winckler, Razif Gabdoulline, Yasmine Alwie, Nidhi Jyotsana, Nadine Kattre, Renate Schottmann, Michaela Scherr, Charu Gupta, Felix F. Adams, Adrian Schwarzer, Dirk Heckl, Axel Schambach, Suzan Imren, R. Keith Humphries, Arnold Ganser, Felicitas Thol, Michael Heuser
Article
Oncology
Christina Rautenberg, Friedrich Stoelzel, Christoph Roellig, Matthias Stelljes, Verena Gaidzik, Michael Lauseker, Oliver Kriege, Mareike Verbeek, Julia Marie Unglaub, Felicitas Thol, Stefan W. Krause, Mathias Haenel, Charlotte Neuerburg, Vladan Vucinic, Christian-Friedrich Jehn, Julia Severmann, Maxi Wass, Lars Fransecky, Jens Chemnitz, Udo Holtick, Kerstin Schaefer-Eckart, Josephine Schroeder, Sabrina Kraus, William Krueger, Ulrich Kaiser, Sebastian Scholl, Kathrin Koch, Lea Henning, Guido Kobbe, Rainer Haas, Nael Alakel, Maximilian-Alexander Roehnert, Katja Sockel, Maher Hanoun, Uwe Platzbecker, Tobias A. W. Holderried, Anke Morgner, Michael Heuser, Tim Sauer, Katharina S. Goetze, Eva Wagner-Drouet, Konstanze Doehner, Hartmut Doehner, Christoph Schliemann, Johannes Schetelig, Martin Bornhaeuser, Ulrich Germing, Thomas Schroeder, Jan Moritz Middeke
Summary: The study found that CPX-351 is an effective treatment for therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes, especially for patients undergoing allogeneic hematopoietic cell transplantation. However, patients may experience significant non-hematologic toxicities during treatment.
BLOOD CANCER JOURNAL
(2021)
Review
Oncology
Sagarajit Mohanty, Michael Heuser
Summary: Acute myeloid leukemia is a biologically diverse blood cancer with variable prognosis, and comprehensive sequencing and mouse models play crucial roles in understanding the genetic mechanisms and drug targets in AML. This review focuses on the leukemogenic function of mutations in seven functional gene groups using evidence from mouse models, providing insights into the cooperative mutations in AML development and their correlation with prognosis.
Article
Biochemistry & Molecular Biology
Eline Gall, Florian Stieglitz, Andreas Pich, Georg Martin Norbert Behrens, Joachim Kuhn, Rainer Blasczyk, Funmilola Josephine Haukamp, Christina Bade-Doeding
Summary: Type B adverse drug reactions pose a significant threat to patients due to their unpredictable occurrence. In the treatment of HIV-positive patients, a severe immune reaction known as Abacavir Hypersensitivity Syndrome (AHS) can arise, which is strongly correlated to a specific gene. However, not all patients carrying this gene are affected by the reaction, suggesting the involvement of other factors. By classifying patients based on their gene profile and analyzing the cellular proteome, potential biomarkers for predicting drug susceptibility have been identified.
Article
Biology
Miriam Laubert, Agnes Bonifacius, Anna Christina Dragon, Caroline Mangare, Rainer Blasczyk, Jochen Huehn, Britta Eiz-Vesper
Summary: This study investigates the impact of vitamin C on virus-specific T cells, showing that vitamin C can increase the activation state of these cells, especially in male donors and donors above 40 years of age. This suggests the potential application of vitamin C as an additional selection criterion and strategy to improve virus-specific T-cell therapy.
Article
Biochemistry & Molecular Biology
Jessica Schneider, Leonie Kuhlmann, Yankai Xiao, Solaiman Raha, Gunter Bernhardt, Michael Stadler, Felicitas Thol, Michael Heuser, Matthias Eder, Arnold Ganser, Sarina Ravens, Reinhold Forster, Immo Prinz, Christian Koenecke, Christian R. Schultze-Florey
Summary: Donor lymphocyte infusion (DLI) can induce durable remission in relapsing patients after alloHSCT, but it carries the risk of graft-versus-host disease (GVHD). This study analyzed T cells in patients receiving DLI after alloHSCT and found that GVHD was associated with changes in the T-cell receptor (TCR) repertoire. The dynamics of CD4(+)CD25(+)CD127(low) regulatory T cells (T-reg cells) and CD4(+) conventional T cells (T-con cells) TCR repertoire could be helpful in diagnosing and monitoring GVHD following DLI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Oncology
June Takeda, Kenichi Yoshida, Masahiro M. Nakagawa, Yasuhito Nannya, Akinori Yoda, Ryunosuke Saiki, Yotaro Ochi, Lanying Zhao, Rurika Okuda, Xingxing Qi, Takuto Mori, Ayana Kon, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Ming-Chung Kuo, Cassandra Kerr, Yasunobu Nagata, Daisuke Morishita, Nobuhiro Hiramoto, Akira Hangaishi, Hideyuki Nakazawa, Ken Ishiyama, Satoru Miyano, Shigeru Chiba, Yasushi Miyazaki, Toshiyuki Kitano, Kensuke Usuki, Nobuo Sezaki, Hisashi Tsurumi, Shuichi Miyawaki, Jaroslaw P. Maciejewski, Takayuki Ishikawa, Kazuma Ohyashiki, Arnold Ganser, Michael Heuser, Felicitas Thol, Lee-Yung Shih, Akifumi Takaori-Kondo, Hideki Makishima, Seishi Ogawa
Meeting Abstract
Biophysics
C. Craddock, U. Platzbecker, M. Heuser, V. Pullarkat, S. Chaudhury, D. Wu, S. Addo, B. Chyla, Q. Jiang, P. Lee, J. E. Wolff
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
June Takeda, Kenichi Yoshida, Masahiro M. Nakagawa, Yasuhito Nannya, Akinori Yoda, Ryunosuke Saiki, Yotaro Ochi, Lanying Zhao, Rurika Okuda, Xingxing Qi, Takuto Mori, Ayana Kon, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Ming-Chung Kuo, Cassandra M. Kerr, Yasunobu Nagata, Daisuke Morishita, Nobuhiro Hiramoto, Akira Hangaishi, Hideyuki Nakazawa, Ken Ishiyama, Satoru Miyano, Shigeru Chiba, Yasushi Miyazaki, Toshiyuki Kitano, Kensuke Usuki, Nobuo Sezaki, Hisashi Tsurumi, Shuichi Miyawaki, Jaroslaw P. Maciejewski, Takayuki Ishikawa, Kazuma Ohyashiki, Arnold Ganser, Michael Heuser, Felicitas Thol, Lee-Yung Shih, Akifumi Takaori-Kondo, Hideki Makishima, Seishi Ogawa
Summary: This study reveals the significant role of gains, amplifications, and mutations of EPOR and JAK2 in the pathogenesis of pure erythroleukemia. The frequent response of these cases to ruxolitinib highlights the potential therapeutic role of JAK2 inhibition for erythroleukemia with EPOR/JAK2-involving lesions.
BLOOD CANCER DISCOVERY
(2022)
Meeting Abstract
Transplantation
Nicole Brueder, Jan T. Kielstein, Luca-Marie Heinze, Catherina Lueck, Victoria Panagiota, Elke Dammann, Sophia Koehler, Steven Talbot, Michael Stadler, Michael Heuser, Arnold Ganser, Matthias Eder, Gernot Beutel
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)