Article
Gastroenterology & Hepatology
Yuli Lin, Qian Cai, Yu Chen, Tiancong Shi, Weiren Liu, Li Mao, Bo Deng, Zhen Ying, Yuan Gao, Haoyang Luo, Xuguang Yang, Xiaowu Huang, Yinghong Shi, Rui He
Summary: This study demonstrates that cancer-associated fibroblasts (CAFs) promote cancer stemness by regulating myeloid-derived suppressor cells (MDSCs) in intrahepatic cholangiocarcinoma (ICC). The 5-LO/LTB4-BLT2 axis may serve as promising therapeutic targets for overcoming ICC chemoresistance by targeting cancer stemness.
Review
Oncology
Jennifer Cao, Lyndah Chow, Steven Dow
Summary: Tumor immune evasion and drug resistance are associated with immune suppressive cellular responses, particularly in metastatic tumors. Modulating the myeloid cell compartment of the tumor microenvironment (TME) can enhance anti-tumoral immunity and improve the effectiveness of immunotherapies. This review examines strategies targeting myeloid suppressor cells in the TME to improve tumor responses to immunotherapy.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jie Zhao, Yiting Dong, Yundi Zhang, Jie Wang, Zhijie Wang
Summary: This article systematically reviews the complex functions of tumor-associated myeloid cells (TAMCs) in tumor development and immune response, and summarizes clinical strategies to overcome resistance to immunotherapy and future research prospects.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Multidisciplinary Sciences
Jingying Zhou, Huanyu Wang, Ting Shu, Jing Wang, Weiqin Yang, Jingqing Li, Lipeng Ding, Man Liu, Hanyong Sun, John Wong, Paul Bo-san Lai, Shun-Wa Tsang, Simon E. Ward, King-Lau Chow, Joseph Jao-yiu Sung, Alfred Sze-Lok Cheng
Summary: Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20 in hepatocellular carcinoma correlates with reduced patient survival and low immunotherapy responsiveness. Here, we showed that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC. Inactivation of Ccrk in myeloid cells confers a mature phenotype and increases IL-12 production, leading to reduced tumor growth and prolonged survival. Mechanistically, CCRK activates STAT3/E4BP4 signaling to induce immunosuppression. Our findings provide insights into MDSC-mediated immunosuppression and offer a potential kinase-target for cancer immunotherapy.
Article
Immunology
Sining Zhu, Almin I. Lalani, Juan Jin, Derek Sant'Angelo, Lori R. Covey, Kebin Liu, Howard A. Young, Suzanne Ostrand-Rosenberg, Ping Xie
Summary: Myeloid-derived suppressor cells (MDSCs), recognized as a prime therapeutic target in cancer, are found to be critically restrained by the adaptor protein TRAF3, which inhibits MDSC expansion via both cell-intrinsic and cell-extrinsic mechanisms. This study provides novel insights into the complex regulatory mechanisms of MDSC expansion and opens up unique perspectives for targeting MDSCs in cancer patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Vinzeigh N. Leukes, Stephanus T. Malherbe, Andriette Hiemstra, Leigh A. Kotze, Kelly Roos, Alana Keyser, Dalene De Swardt, Andrea Gutschmidt, Gerhard Walzl, Nelita du Plessis
Summary: Resistance to common anti-TB drugs is a major challenge in TB treatment, leading to the investigation of host-directed therapies (HDTs). This study found that Sildenafil, when repurposed as an HDT, was unable to reverse the suppressive effects of MDSC on T-cell responsiveness, suggesting the need for further development of MDSC-targeting HDTs for TB.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Heejin Lim, Taewoo Yang, Wongeun Lee, Sung-Gyoo Park
Summary: The study demonstrates that MDSCs are a source of MFGE8, which plays a role in tumor metastasis. TME positively regulates MFGE8 production by MDSCs through TGF-beta, suggesting MFGE8 as an important effector molecule for MDSCs to promote tumor metastasis.
Article
Immunology
Ina N. Eckert, Eliana Ribechini, Katja J. Jarick, Sandra Strozniak, Sarah J. Potter, Andreas Beilhack, Manfred B. Lutz
Summary: The study discovered that the adhesion of VLA-1 integrin to collagen IV plays a critical role in extending the contact time between MDSCs and T cells, which is necessary for suppression.
FRONTIERS IN IMMUNOLOGY
(2021)
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.
Article
Oncology
Sergio Ortiz-Espinosa, Xabier Morales, Yaiza Senent, Diego Alignani, Beatriz Tavira, Irati Macaya, Borja Ruiz, Haritz Moreno, Ana Remirez, Cristina Sainz, Alejandro Rodriguez-Pena, Alvaro Oyarbide, Mikel Ariz, Maria P. Andueza, Karmele Valencia, Alvaro Teijeira, Kai Hoehlig, Axel Vater, Barbara Rolfe, Trent M. Woodruff, Jose Maria Lopez-Picazo, Silvestre Vicent, Grazyna Kochan, David Escors, Ignacio Gil-Bazo, Jose Luis Perez-Gracia, Luis M. Montuenga, John D. Lambris, Carlos Ortiz de Solorzano, Fernando Lecanda, Daniel Ajona, Ruben Pio
Summary: This study reveals that C5a can enhance the capacity of PMN-MDSCs to promote tumor growth and metastasis by inducing the formation of NETs. The formation of NETs is dependent on the production of HMGB1 by cancer cells. Inhibiting C5a, C5aR1, or NETosis can reduce the number of circulating tumor cells and the metastatic burden in a mouse lung metastasis model. The translational relevance of these findings is supported by the stimulation of migration and NETosis in PMN-MDSCs obtained from lung cancer patients.
Review
Oncology
Zhaonian Hao, Ruyuan Li, Yuanyuan Wang, Shuangying Li, Zhenya Hong, Zhiqiang Han
Summary: MDSC play vital roles in cancer microenvironment, influencing the responses to immunotherapies and prognosis of cancer patients. Therefore, proposing MDSC-inhibiting strategies becomes crucial in the field of cancer immunotherapies.
BIOMARKER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tracy W. Liu, Seth T. Gammon, Ping Yang, David Fuentes, David Piwnica-Worms
Summary: The myeloid-derived cells produce HOCl which inhibits IKK activity in melanoma tumor cells, leading to antitumor responses during early tumor growth. The MDC-derived HOCl mediates changes in gene expression and signaling pathways, enhancing immune response and reducing tumor growth.
Article
Immunology
Zhuwan Lyu, Bingyuan Huang, Jun Zhang, Qiwei Qian, Xiting Pu, Nana Cui, Yiyan Ou, Bo Li, Zhengrui You, Min Lian, Ruqi Tang, Weihua Chen, Zhicong Zhao, Jiajie Hou, M. Eric Gershwin, Haiyan Zhang, Qiang Xia, Xiong Ma
Summary: This study reveals the critical role of N6-methyladenosine (m6A) reader YTHDF2 in myeloid-derived suppressor cells (MDSC) and its impact on autoimmune hepatitis (AIH). The loss of YTHDF2 leads to increased MDSCs, particularly PMN-MDSCs, in the liver and bone marrow. YTHDF2 deficiency attenuates concanavalin (ConA)-induced liver injury by promoting MDSC expansion and chemotaxis. Additionally, YTHDF2 upregulation is observed in the livers of AIH patients.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Pharmacology & Pharmacy
Shweta Joshi, Andrew Sharabi
Summary: This review discusses the role of MDSCs in tumor growth, their interaction with NK cells, and the impact on NK cell-based immunotherapies, presenting strategies to enhance NK cell cytotoxicity.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Jessica Filtjens, Anais Roger, Linda Quatrini, Elisabeth Wieduwild, Jordi Gouilly, Guillaume Hoeffel, Rafaelle Rossignol, Clara Daher, Guilhaume Debroas, Sandrine Henri, Claerwen M. Jones, Bernard Malissen, Laura K. Mackay, Aziz Moqrich, Francis R. Carbone, Sophie Ugolini
Summary: The study demonstrates that Nav(1.8)(+) sensory neurons play a crucial role in regulating CD8 T cell immune responses against HSV-1 infection, affecting skin damage severity and cytokine production. Sensory neurons are also involved in controlling neutrophil infiltration and dendritic cell responses, highlighting their potential as a therapeutic target.
NATURE COMMUNICATIONS
(2021)