Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Article
Oncology
Deli Mao, Zhijun Zhou, Hengxing Chen, Xinran Liu, Dongsheng Li, Xiancong Chen, Yulong He, Mingyang Liu, Changhua Zhang
Summary: PLEK2 suppresses NK cell immune surveillance by promoting MICA shedding, which serves as a potential therapeutic target for gastric cancer.
Review
Immunology
Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: Immune checkpoint inhibitors have revolutionized immuno-oncology by achieving durable immune control of cancer, however, tumor immune evasion mechanisms pose a challenge for treatment development. Combination therapies targeting NK cell-activating receptors like NKG2D are emerging as frontrunners in immuno-oncology, with strategies to boost MICA/B expression and inhibit their shedding being proposed for enhancing antitumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Abigael Eva Chaouat, Barbara Seliger, Ofer Mandelboim, Dominik Schmiedel
Summary: The coevolution of human immune system and herpesviruses led to the emergence of cellular danger molecules and viral countermeasures. HHV-6A encodes immunoevasins U20 and U21 to suppress NKG2D ligands ULBP1 and ULBP3, impairing immune recognition. The study highlights the evolutionary conserved immune escape mechanisms of HHV-6A and HHV-6B towards NKG2D ligands.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Yan Zhang, Ruimin Hu, Bixin Xi, Dimin Nie, Hanxiao Xu, Aiguo Liu
Summary: Low-dose chemotherapy induces senescence in neuroblastoma cells, promoting the shedding of NKG2D ligand MICA/B through the MALAT1/miR-92a/ADAM10 axis, thereby contributing to the formation of a suppressive immune microenvironment and promoting immune escape.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Hui Ding, Garrett W. Buzzard, Sisi Huang, Michael G. Sehorn, R. Kenneth Marcus, Yanzhang Wei
Summary: The study created a fusion protein that combines the stress signal protein MICA to activate NK cells, and the G129R variant to target PRLR-positive breast cancer cells. This fusion protein can activate NK cells to kill PRLR-positive breast cancer cells and enhance the cytotoxicity of NK cells.
Review
Medicine, Research & Experimental
Zhenhui Wu, Huan Zhang, Min Wu, Guorui Peng, Yanqiu He, Na Wan, Yingjian Zeng
Summary: The NKG2D/NKG2D-L axis plays a crucial role in the development of AML, activating the immune system and affecting chemotherapy and immune recognition. Therefore, research targeting the NKG2D/NKG2D-L axis holds great potential for the discovery of novel biomacromolecule antibodies and pharmacological modulators.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Florencia Secchiari, Sol Yanel Nunez, Jessica Mariel Sierra, Andrea Ziblat, Maria Victoria Regge, Ximena Lucia Raffo Iraolagoitia, Agustin Rovegno, Carlos Ameri, Fernando Pablo Secin, Nicolas Richards, Hernando Rios Pita, Gonzalo Vitagliano, Luis Rico, Mauro Mieggi, Florencia Frascheri, Nicolas Bonanno, Leandro Blas, Aldana Trotta, Adrian David Friedrich, Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: NKG2D is an important activating receptor of natural killer (NK) cells that recognizes multiple ligands, including MICA. This study found that MICA is overexpressed in renal cell carcinoma (RCC) and is associated with decreased overall survival in RCC patients. Both tumor cells and tumor-infiltrating leukocytes showed increased MICA expression, while peripheral blood NK cells exhibited downregulated NKG2D. Furthermore, these NKG2D-expressing tumor-infiltrating NK cells displayed functional impairment and altered metabolic fitness.
Review
Oncology
Jing Zhang, Qizhi Luo, Xin Li, Junshuang Guo, Quan Zhu, Xiaofang Lu, Leiyan Wei, Zhiqing Xiang, Manqing Peng, Chunlin Ou, Yizhou Zou
Summary: This article summarizes the new mechanism of immune escape in the ncRNA-related MICA/NKG2D pathway. miRNAs target the 3'-UTR of NKG2D and MICA mRNA to inhibit translation and promote degradation, while circRNAs, lncRNAs, and mRNAs mediate abnormal MICA expression by competing with miRNAs. These findings provide insights into the potential application of ncRNAs in immunotherapy and cancer treatment.
BIOMARKER RESEARCH
(2023)
Article
Immunology
Nadia D. Milito, Alessandra Zingoni, Helena Stabile, Alessandra Soriani, Cristina Capuano, Marco Cippitelli, Angela Gismondi, Angela Santoni, Rossella Paolini, Rosa Molfetta
Summary: The activation of natural killer (NK) cells is influenced by activating and inhibitory receptors which aid in identifying diseased cells. Among these receptors, NKG2D and DNAM-1 are crucial for the immune response against cancer as they bind to ligands expressed on transformed cells. However, during tumor progression, these receptors are often downregulated and lose their functionality. NKG2D internalization has been associated with dysfunctional phenotype characterized by tolerance to other activating receptors. Nevertheless, the consequences of NKG2D engagement are still incompletely understood. In this study, we demonstrate that NKG2D engagement impairs DNAM-1-mediated killing on human NK cells through two converging mechanisms: upregulation of the inhibitory receptor TIGIT, which suppresses DNAM-1-mediated cytotoxic function, and direct inhibition of DNAM-1 signaling. These findings reveal a novel interplay between NKG2D and DNAM-1/TIGIT receptors that may enable neoplastic cells to evade clearance by NK cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Oncology
Muthulekha Swamydas, Elena Murphy, James J. Ignatz-Hoover, Ehsan Malek, James J. Driscoll
Summary: Multiple myeloma is an incurable cancer that can evade host immune surveillance and resist current treatments through various intrinsic and extrinsic mechanisms. Understanding the immune escape mechanisms can aid in developing novel strategies to improve patient survival.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Medicine, Research & Experimental
Kerry A. Whalen, Kavya Rakhra, Naveen K. Mehta, Alexander Steinle, Jennifer S. Michaelson, Patrick A. Baeuerle
Summary: The field of immuno-oncology has revolutionized cancer patient care, but there are still challenges with current therapeutic approaches targeting T cells. Engaging the innate immune system, especially natural killer (NK) cells, has emerged as a promising modality in immunotherapy. This review focuses on therapeutic strategies that selectively engage NK cells for cancer therapy, particularly targeting the activating receptors NKG2D and CD16A.
Article
Biochemical Research Methods
Xiaoming Zhong, Hongqun Liao, Shaowen Hu, Kaiyuan Luo, Huifang Zhu
Summary: The natural product adenanthin significantly promotes the expression of NKG2D ligands in hepatoma cells, improving the killing activity of NK cells against liver cancer cells. This study is the first to report the anti-cancer effects of adenanthin mediated by indirect activation of NK cells. Adenanthin may be used as a sensitizing agent for NK cells in tumor immunotherapy.
MOLECULAR AND CELLULAR PROBES
(2021)
Review
Immunology
Barbara Seliger, Ulrike Koehl
Summary: This article provides an overview of NK cell biology, the impact of tumor cells and the tumor microenvironment on NK cells, and the latest advancements in NK cell-based therapeutic strategies. The article emphasizes the challenges of tumor cells evading NK cell recognition and NK cell immune suppression, and highlights the need to explore and improve treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fernanda Scopelliti, Valentina Dimartino, Caterina Cattani, Andrea Cavani
Summary: This study found that TRPA1 channels are highly expressed in the CD56(dim)CD16(+) subpopulation of NK cells, and their activation can increase cell-mediated cytotoxicity against tumors while also regulating the survival of NK cells to limit excessive cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)