Review
Immunology
Claudia Giannotta, Federica Autino, Massimo Massaia
Summary: Myeloid derived suppressor cells (MDSC) have significant roles in regulating immune homeostasis and immune responses, especially in cancer. MDSC interact with cancer cells in the tumor microenvironment through various mechanisms such as producing soluble factors, expressing inhibitory molecules, rewiring metabolism, and releasing exosomes. The relationship between MDSC and tumor cells leads to immune evasion and cancer growth. In multiple myeloma (MM), MDSC play a major role in creating a tumor-promoting microenvironment. This minireview discusses the interplay between MDSC and MM microenvironment, as well as potential strategies to target MDSC.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Fatih M. Uckun
Summary: T-cell engaging bispecific antibodies (BsABs) have the potential to delay disease progression in multiple myeloma by redirecting host T-cell cytotoxicity towards malignant MM clones and immunosuppressive myeloid-derived suppressor cells in the bone marrow microenvironment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Haomin Yan, Tomohiro Kawano, Hideaki Kanki, Kumiko Nishiyama, Munehisa Shimamura, Hideki Mochizuki, Tsutomu Sasaki
Summary: In this study, prophylactic anti-Ly6G antibody administration was found to have a protective effect against ischemic stroke by reducing activated neutrophil infiltration and neutrophil extracellular trap formation in the brain parenchyma, as well as suppressing polymorphonuclear myeloid-derived suppressor cell accumulation. This study may provide a novel therapeutic approach for ischemic stroke.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Immunology
Alexander Glover, Zhaoqin Zhang, Claire Shannon-Lowe
Summary: Myeloid derived suppressor cells (MDSCs) are a heterogenous population of myeloid cells derived from monocyte and granulocyte precursors. They are pathologically expanded in conditions of ongoing inflammation where they function to suppress both innate and adaptive immunity. They are associated with inhibition of the anti-tumour immune response in cancer and are universally associated with a poor prognosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Kentaro Mizuhara, Yuji Shimura, Taku Tsukamoto, Akinori Kanai, Saeko Kuwahara-Ota, Junko Yamaguchi, Ayako Muramatsu, Haruya Okamoto, Yoko Taminishi-Katsuragawa, Yuka Kawaji-Kanayama, Reiko Isa, Shinsuke Mizutani, Toshiya Inaba, Junya Kuroda
Summary: In multiple myeloma, the shift of the tumour immune microenvironment to a suppressive state promotes disease development and resistance to immunotherapy. This study demonstrates that miR-106a-5p and miR-146a-5p delivered by tumour-derived exosomes play essential roles in inducing monocyte-derived suppressor cells in multiple myeloma. These miRNAs collaborate with CCL5 and MIF to promote the induction of suppressor cells. This finding may contribute to the development of novel therapeutic approaches to improve the efficacy of immunotherapy.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Guohui Qin, Shasha Liu, Li Yang, Weina Yu, Yi Zhang
Summary: Variation in myeloid cell differentiation is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. Single-cell sequencing reveals the differentiation trajectory of myeloid cells in COVID-19 patients. Targeting myeloid cell-derived cytokines or checkpoints is crucial in developing therapeutic strategies for severe COVID-19 patients.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Review
Immunology
Samantha L. Tucker, Demba Sarr, Balazs Rada
Summary: Cystic Fibrosis is a genetic disease that causes chronic lung inflammation and infections, leading to high mortality rates. Immune system disruption in CF results in impaired immune responses, chronic infections with pathogens, and alterations in T cell and neutrophil functions. The role of P. aeruginosa and gMDSCs in T cell suppression and immune evasion in CF remains a subject of ongoing research.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Geriatrics & Gerontology
Qianling Jiang, Jielin Duan, Luc Van Kaer, Guan Yang
Summary: Myeloid-derived suppressor cells (MDSCs), a heterogeneous cell population consisting mostly of immature myeloid cells, have been found to play a role in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Accumulation of MDSCs has been observed in inflamed tissues and lymphoid organs of MS patients and EAE mice, but their contribution to the pathogenesis of MS/EAE remains unclear. This review aims to summarize our current understanding of MDSC subsets and their potential roles in MS/EAE pathogenesis. We also discuss the potential utility and obstacles in using MDSCs as biomarkers and cell-based therapies for MS.
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)
Article
Oncology
Rong Fan, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Philip Vlummens, Anke Maes, Catharina Muylaert, Elke De Bruyne, Eline Menu, Holly Evans, Andrew Chantry, Nathan De Beule, Dirk Hose, Marie Toerngren, Helena Eriksson, Karin Vanderkerken, Ken Maes, Karine Breckpot, Kim De Veirman
Summary: This study reveals the dual therapeutic effects of the immunomodulator tasquinimod in multiple myeloma patients, including inhibition of tumor cell proliferation and promotion of immune activity. The results suggest that tasquinimod can inhibit immunosuppressive myeloid cells in the bone marrow by targeting S100A9, and enhance T cell activity and functionality.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Christopher Groth, Rebekka Weber, Samantha Lasser, Feyza Gul Ozbay, Annina Kurzay, Vera Petrova, Peter Altevogt, Jochen Utikal, Viktor Umansky
Summary: This review summarizes the origin of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and their relation to classical neutrophils, outlining their metastasis promoting features and promising strategies for targeting them to enhance the efficacy of cancer immunotherapy.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Medicine, Research & Experimental
Anik Pramanik, Sankar Bhattacharyya
Summary: The MDSC population in the tumor microenvironment plays a crucial role in tumor immune evasion and cancer progression by disrupting antitumor T cell activity and potentially affecting other immune cell functions.
Article
Medicine, General & Internal
Mi-Hyun Bae, Chan-Jeoung Park, Cheolwon Suh
Summary: MDSCs in patients with myeloma have prognostic significance, with their levels in both blood and bone marrow associated with disease progression. Patients with high levels of PB-mMDSCs have poorer prognosis. This study highlights the independent adverse prognostic impact of PB-mMDSCs in patients with myeloma.
JOURNAL OF CLINICAL MEDICINE
(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
Medicine, General & Internal
Suncica Kapor, Juan F. Santibanez
Summary: This review discusses the main features of MDSCs and MSCs in myeloid malignancies, revealing that MDSCs are elevated in numbers and exhibit strong immunosuppressive capabilities, while MSCs not only have immunosuppressive properties but also regulate the growth, apoptosis, and chemotherapy resistance of myeloid leukemia cells.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medical Laboratory Technology
Hui Chen, Zhao Li, Sheng Feng, Melissa Richard-Greenblatt, Emily Hutson, Stefen Andrianus, Laurel J. Glaser, Kyle G. Rodino, Jianing Qian, Dinesh Jayaraman, Ronald G. Collman, Abigail Glascock, Frederic D. Bushman, Jae Seung Lee, Sara Cherry, Alejandra Fausto, Susan R. Weiss, Hyun Koo, Patricia M. Corby, Alfonso Oceguera, Una O'Doherty, Alfred L. Garfall, Dan T. Vogl, Edward A. Stadtmauer, Ping Wang
Summary: The study developed a high-sensitivity SARS-CoV-2 antigen detection assay to track antigen burden in respiratory samples from different populations. Results showed that the assay accurately detects acute infections, with different outcomes observed in immunocompetent and immunocompromised patients, making it useful for screening and monitoring patients' antigen burden.
CLINICAL CHEMISTRY
(2022)
Letter
Oncology
Alfred Garfall, Adam Cohen, Edward Stadtmauer, Sandra Susanibar-Adaniya, Dan Vogl, Adam Waxman
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Angela Dispenzieri, Amrita Krishnan, Bonnie Arendt, Beth Blackwell, Paul K. Wallace, Surendra Dasari, Dan T. Vogl, Yvonne Efebera, Mingwei Fei, Nancy Geller, Sergio Giralt, Theresa Hahn, Alan Howard, Mindy Kohlhagen, Heather Landau, Parameswaran Hari, Marcelo C. Pasquini, Muzaffar H. Qazilbash, Philip McCarthy, Nina Shah, David H. Vesole, Edward Stadtmauer, David Murray
Summary: Measuring response is crucial for multiple myeloma patients, and Mass-Fix and MRD have been identified as effective indicators for predicting survival outcomes.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
Hui Deng, Cindy Lin, Laura Garcia-Gerique, Shuyu Fu, Zachary Cruz, Erin E. Bonner, Matthew Rosenwasser, Sridharan Rajagopal, M. Naveen Sadhu, Chandru Gajendran, Mohd Zainuddin, Ramachandraiah Gosu, Dhanalakshmi Sivanandhan, Miriam A. Shelef, Brian Nam, Dan T. Vogl, Dmitry I. Gabrilovich, Yulia Nefedova
Summary: PAD4 plays a critical role in neutrophil migration in cancer, and targeting PAD4 with a small molecule inhibitor can suppress tumor growth and metastasis and enhance the efficacy of immune checkpoint blockade therapy.
Meeting Abstract
Hematology
Brian Hoeynck, Wei-Ting Hwang, Alfred L. Garfall, Sandra Patricia Susanibar-Adaniya, Dan T. Vogl, Adam Waxman, Edward A. Stadtmauer, Adam D. Cohen
Meeting Abstract
Hematology
Adam D. Cohen, Alfred L. Garfall, Sandra Patricia Susanibar-Adaniya, Dan T. Vogl, Adam Waxman, Oksana De Mesa, Elizabeth Kane, Charles Nichols, Beatrice Razzo, Edward A. Stadtmauer
Article
Oncology
Mark A. Dawson, Gautam Borthakur, Brian J. P. Huntly, Anastasios Karadimitris, Adrian Alegre, Aristeidis Chaidos, Dan T. Vogl, Daniel A. Pollyea, Faith E. Davies, Gareth J. Morgan, Jacob L. Glass, Manali Kamdar, Maria -Victoria Mateos, Natalia Tovar, Paul Yeh, Regina Garcia Delgado, Faisal Basheer, Ludovica Marando, Paolo Gallipoli, Anastasia Wyce, Anu Shilpa Krishnatry, Olena Barbash, Evi Bakirtzi, Geraldine Ferron-Brady, Natalie O. Karpinich, Michael T. McCabe, Shawn W. Foley, Thierry Horner, Arindam Dhar, Brandon E. Kremer, Michael Dickinson
Summary: Molibresib, a selective inhibitor of BET proteins, was evaluated as a monotherapy for hematological malignancies. The study consisted of dose escalation to determine the recommended dose and dose expansion to assess safety and efficacy in relapsed/refractory MDS and CTCL patients. Results showed limited antitumor activity and significant toxicities, suggesting the need for combination regimens with molibresib.
CLINICAL CANCER RESEARCH
(2023)
Article
Hematology
Brian W. Hoeynck, Adam D. Cohen, Edward A. Stadtmauer, Sandra P. Susanibar-Adaniya, Dan T. Vogl, Adam J. Waxman, Mark Bardsley, Samantha Le, Lexis LaMaestra, Alfred L. Garfall
Summary: Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal disease that affects the central nervous system. It is caused by the reactivation of the JC virus in individuals with weakened immune systems such as those with HIV, cancer, or taking immunosuppressive medications. PML has been rarely reported in multiple myeloma patients, and this study describes six cases of PML among multiple myeloma patients treated at a specific institution between 2013 and 2022, including two cases associated with recently developed BCMA-directed immunotherapies.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Genetics & Heredity
Ernest J. J. Nelson, Maria A. A. Gubbiotti, Alicia M. M. Carlin, MacLean P. P. Nasrallah, Vivianna M. M. Van Deerlin, Sarah E. E. Herlihy
Summary: This study evaluated the addition of a rapid real-time PCR assay to the testing algorithm for determining the IDH mutational status in glioma patients. The results showed that the RT-PCR assay had 100% concordance with immunohistochemistry and sequencing studies, and had a faster turnaround time compared to sequencing studies (average 2.6 days). Therefore, this RT-PCR assay can be reliably implemented for determining the IDH mutation status in glioma patients.
MOLECULAR DIAGNOSIS & THERAPY
(2023)
Letter
Oncology
Xinhe Shan, Qi Long, Alfred L. Garfall, Sandra P. Susanibar-Adaniya
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Alfred L. Garfall, Adam D. Cohen, Sandra P. Susanibar-Adaniya, Wei-Ting Hwang, Dan T. Vogl, Adam J. Waxman, Simon F. Lacey, Vanessa E. Gonzalez, Joseph A. Fraietta, Minnal Gupta, Irina Kulikovskaya, Lifeng Tian, Fang Chen, Natalka Koterba, Robert L. Bartoszek, Margaret Patchin, Rong Xu, Gabriela Plesa, Don L. Siegel, Andrea Brennan, Anne Marie Nelson, Regina Ferthio, Angela Cosey, Kim-Marie Shea, Rachel Leskowitz, Megan Four, Wesley Wilson, Fei Miao, Eric Lancaster, Beatriz M. Carreno, Gerald P. Linette, Elizabeth O. Hexner, Regina M. Young, Dexiu Bu, Keith G. Mansfield, Jennifer L. Brogdon, Carl H. June, Michael C. Milone, Edward A. Stadtmauer
Summary: This study conducted a clinical trial of CAR T cells in multiple myeloma patients and found that it can be a safe and effective treatment for the disease. The results demonstrate the relationship between early treatment and CAR T cell reexpansion and durable clinical response.
BLOOD CANCER DISCOVERY
(2023)
Article
Oncology
Kavita M. Dhodapkar, Adam D. Cohen, Akhilesh Kaushal, Alfred L. Garfall, Renee Julia Manalo, Allison R. Carr, Samuel S. McCachren III, Edward A. Stadtmauer, Simon F. Lacey, J. Joseph Melenhorst, Carl H. June, Michael C. Milone, Madhav Dhodapkar
Summary: This study combined multiple approaches to study the tumor/immune cells in the tumor microenvironment of myeloma patients before and after BCMA CAR T therapy. The findings suggest that lower diversity of T-cell receptor repertoire, presence of hyperexpanded clones and exhausted phenotype, as well as the presence of specific cells in the bone marrow are associated with shorter progression-free survival following therapy. Conversely, longer progression-free survival is associated with an increased proportion of certain cells and the emergence of cells expressing marrow-residence genes. Tumor recurrence is associated with the emergence of new dominant clones.
BLOOD CANCER DISCOVERY
(2022)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.