Review
Biology
Ge Tan, Katelyn M. Spillane, John Maher
Summary: The human NKG2D ligand family consists of eight stress-induced molecules. These ligands are expressed by over 80% of human cancers, but can also have immunosuppressive effects due to shedding, release via exosomes, and intracellular trapping. NKG2D deficiency in mice increases susceptibility to some types of cancer, indicating its role in immune surveillance for malignancy.
Article
Cell Biology
Milena Ivanova, Gergana Tsvetkova, Spaska Lessichkova, Nevena Gesheva, Evgueniy Hadjiev, Velizar Shivarov
Summary: JAK2 V617F-driven myeloproliferative neoplasms (MPNs) can evade immune surveillance by up-regulating PD-L1 and down-regulating HLA class I pathway. In addition, the role of major histocompatibility complex class I-related genes (MICA and MICB) in JAK2 V617F+ MPNs was assessed. Two protective alleles, MICA*008:01 and MICA*016, were identified through high resolution genotyping. MPN patients had increased levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes showed higher surface expression of MICB, while the expression of MICA and MICB transcripts did not differ from normal granulocytes. MICA and MICB genes were down-regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients compared to normal CD34+ hematopoietic stem cells. These findings suggest that MICA and MICB genes play a minor but significant role in the development of MPNs, and targeted MICA approaches may be beneficial for certain patients.
Review
Immunology
Alena Machuldova, Monika Holubova, Valentina S. Caputo, Miroslava Cedikova, Pavel Jindra, Lucie Houdova, Pavel Pitule
Summary: Natural killer cells (NK cells) play key roles in malignant diseases, particularly in acute myeloid leukemia. NK cell activity is influenced by signals received through binding of different ligands to activating or inhibitory receptors. NK cells eliminate transformed or infected cells by binding to NKG2D ligands, while target cells develop protective mechanisms to evade NK cell killing.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Milena Ivanova, Bushra Al Hadra, Stanislav Yordanov, Spaska Lesichkova, Hristo Stoyanov, Velizar Shivarov, Elitsa Deliverska
Summary: The study identified significant protective effects of MICB*002:01 and increased frequencies of MICB*018, *019, and *020 alleles in Oral Squamous Cell Carcinoma patients. A predisposing association for the MICA*008:01-MICB*019 haplotype was also observed. Correlations were found between functionally relevant MICA polymorphisms and soluble MICA levels.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2021)
Article
Medicine, General & Internal
Alena Machuldova, Lucie Houdova, Katerina Kratochvilova, Martin Leba, Pavel Jindra, Pavel Ostasov, Diana Maceckova, Robin Klieber, Hana Gmucova, Jiri Sramek, Monika Holubova
Summary: The study examined the impact of genetic variations in MICA-14 and MICB-58 on HSCT outcomes, finding a significant association between grafts from donors with MICA-14Gly allele and worsened patient overall survival, as well as a negative effect of MICB-58 polymorphism on relapse-free survival.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Shuo Wang, Guillaume C. Onyeaghala, Nathan Pankratz, Heather H. Nelson, Bharat Thyagarajan, Weihong Tang, Faye L. Norby, Chinenye Ugoji, Corinne E. Joshu, Christian R. Gomez, David J. Couper, Josef Coresh, Elizabeth A. Platz, Anna E. Prizment
Summary: The study found that MICA and MICB are associated with colorectal cancer development, and low sMICA levels are related to lower risk of colorectal cancer. These findings highlight the importance of immune surveillance in colorectal cancer.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Immunology
Burak Kucuk, Ercan Cacan
Summary: This study analyzed genomic and gene expression data to investigate the regulation of NKG2DLs in lung adenocarcinoma (LUAD). The results showed that NKG2DLs, particularly MICA, were downregulated in LUAD compared to normal samples. Downregulated MICA transcript expression may be a prognostic indicator for LUAD. However, the mechanisms underlying the downregulation of MICA were not clarified in this study.
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
Cell Biology
Satu Koskela, Silja Tammi, Jonna Clancy, Jonathan A. M. Lucas, Thomas R. Turner, Kati Hyvarinen, Jarmo Ritari, Jukka Partanen
Summary: Genetic variation in MICA and MICB genes is associated with transplantation outcome, autoimmune diseases, and infections. This study analyzes the polymorphism and allele distribution of these genes in Finland, a population with historical bottleneck and founder effects. The results show population differences and a relatively high level of polymorphism in MICA and MICB genes, including the discovery of novel alleles with amino acid changes.
Article
Immunology
Nassim Hammoudi, Sarah Hamoudi, Julie Bonnereau, Hugo Bottois, Kevin Perez, Madeleine Bezault, Deborah Hassid, Victor Chardiny, Celine Grand, Brice Gergaud, Joelle Bonnet, Leila Chedouba, My-Linh Tran Minh, Jean-Marc Gornet, Clotilde Baudry, Helene Corte, Leon Maggiori, Antoine Toubert, Jacqueline McBride, Camille Brochier, Margaret Neighbors, Lionel Le Bourhis, Matthieu Allez
Summary: This study developed an ex vivo model to assess lympho-epithelial interactions in Crohn's Disease (CD) patients. The results showed that mucosal T cells from CD patients have a direct deleterious effect on the epithelial cells, while this effect is not observed in controls. This effect can be inhibited by limiting lympho-epithelial interactions.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Cell Biology
Kevin J. Lopez, John Paul Spence, Wei Li, Wenjun Zhang, Barry Wei, Arthur A. Cross-Najafi, James R. Butler, David K. C. Cooper, Burcin Ekser, Ping Li
Summary: This study clarifies the role of pULBP-1 in the interaction between NK cells and pig cells. The results demonstrate that pULBP-1 is not a crucial factor in initiating xenogeneic human NK cell activation.
Article
Rheumatology
A. Mariotte, L. Bernardi, C. Macquin, A. DeCauwer, I Kotova, S. Blueml, D. Noel, A. Scanu, L. Punzi, R. Carapitou, J. Sibilia, S. Bahram, P. Georgel
Summary: The study found marked overproduction of sMICA in the synovial fluid of patients with rheumatoid arthritis. Mouse studies demonstrated the complex transcriptional regulation of Nkg2d ligands encoding genes depending on the inflammatory setting and microenvironment. Quantification of sMICA could be an interesting biomarker for identifying acute inflammation in rheumatoid arthritis patients where classical markers are undetectable.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(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.
Article
Immunology
Xiaolong Wu, Amit Sharma, Johannes Oldenburg, Hans Weiher, Markus Essler, Dirk Skowasch, Ingo G. H. Schmidt-Wolf
Summary: CIK cells are a promising candidate for immunotherapy due to their convenient and relatively inexpensive expansion capability. NKG2D plays a crucial role in CIK cell-mediated antitumor activity, with NKG2D engagement alone being sufficient to activate CIK cells. The role of 2B4 in CIK cells is still unclear, but it provides limited synergy with NKG2D in certain aspects. Additional research is needed to optimize the functional potential of CIK cells for cancer therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pathology
Kasper Vadstrup, Elisabeth Douglas Galsgaard, Helle Jensen, Lewis L. Lanier, James C. Ryan, Shih-Yu Chen, Garry P. Nolan, Marianne Kajbaek Vester-Andersen, Julie Steen Pedersen, Jens Gerwien, Teis Jensen, Flemming Bendtsen
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2017)
Article
Multidisciplinary Sciences
Camilla Melin Furst, Matthias Morgelin, Kasper Vadstrup, Dick Heinegard, Anders Aspberg, Anna M. Blom
Article
Multidisciplinary Sciences
Kasper Vadstrup, Elisabeth Douglas Galsgaard, Jens Gerwien, Marianne Kajbaek Vester-Andersen, Julie Steen Pedersen, Julie Rasmussen, Soren Neermark, Marianne Kiszka-Kanowitz, Teis Jensen, Flemming Bendtsen
Article
Dermatology
Georgios Kokolakis, Kasper Vadstrup, Jes B. Hansen, Jose Manuel Carrascosa
Summary: The study aimed to compare the efficacy of brodalumab and ustekin-umab in patients with moderate-to-severe plaque psoriasis, considering concomitant PsA. The results showed that brodalumab had better performance in achieving complete skin clearance and improving quality of life compared to ustekin-umab, regardless of PsA status.
Article
Gastroenterology & Hepatology
Kasper Vadstrup, Sarah Alulis, Andras Borsi, Tine Rikke Jorgensen, Agnete Nielsen, Pia Munkholm, Niels Qvist
CROHNS & COLITIS 360
(2020)