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killer immunoglobulin like receptors and cancer

Hui Yu, Fang Liu, Benoit Sansas, Bin Kang, Xavier Preville, Xianghua Wu, Jianhua Chang, Romain Micol, Jialei Wang, Xia Meng
Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population...
February 2017: Molecular and Clinical Oncology
Miguel López-Botet, Carlos Vilches, Dolores Redondo-Pachón, Aura Muntasell, Aldi Pupuleku, José Yélamos, Julio Pascual, Marta Crespo
Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection...
2017: Frontiers in Immunology
Pâmela Portela, Joice Merzoni, Juliana D Lindenau, Daniel C Damin, Timothy John Wilson, Rafael Roesler, Gilberto Schwartsmann, Luiz Fernando Jobim, Mariana Jobim
Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls...
March 2017: Human Immunology
Cristina Morales-Estevez, Juan De la Haba-Rodriguez, Barbara Manzanares-Martin, Ignacio Porras-Quintela, Antonio Rodriguez-Ariza, Alberto Moreno-Vega, Maria J Ortiz-Morales, Maria A Gomez-España, Maria T Cano-Osuna, Javier Lopez-Gonzalez, Beatriz Chia-Delgado, Rafael Gonzalez-Fernandez, Enrique Aranda-Aguilar
Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of natural killer cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their human leukocyte antigen (HLA) ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated with the variable response observed to mAbs based anti-epidermal growth factor receptor (EGFR) therapies...
2016: Frontiers in Immunology
Rohtesh S Mehta, Katayoun Rezvani
Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell transplantation, donor NK cells that express an inhibitory KIR for an HLA class I molecule that is absent on recipient targets (KIR/KIR-ligand mismatch), can recognize and react to this missing self and mediate cytotoxicity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
Yayi He, Paul A Bunn, Caicun Zhou, Dan Chan
BACKGROUND: Nature killer (NK) cells are the immune system's first line of defense against both viral infections and tumors. Killer cell immunoglobulin-like receptors (KIRs) are associated with susceptibility to different types of cancers. We investigated KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression and their association with survival in non-small cell lung cancer (NSCLC). METHODS: The expression of KIR 2D (L1, L3, L4, S4) (BC032422/ ADQ31987/ NP_002246/ NP_036446, ABCAM) and KIR 3DL1 (AA 1-444, ABCAM) protein was assessed by immunohistochemistry (IHC) in 62 NSCLC patients...
December 13, 2016: Oncotarget
Koroush Ghanadi, Bahareh Shayanrad, Seyyed Amir Yasin Ahmadi, Farhad Shahsavar, Hossein Eliasy
Colorectal cancer is one of the most common types of inflammation-based cancers and is occurred due to growth and spread of cancer cells in colon and/or rectum. Previously genetic association of cell cycle genes, both proto-oncogenes and the tumor suppressors has been proved. But there were few studies about association of immune related genes such as killer-cell immunoglobulin-like receptors (KIRs). Thus we intend to perform a meta-analysis to find the association of different genes of KIR and susceptibility to be affected by colorectal cancer...
December 2016: Genomics Data
Wei Wang, Amy K Erbe, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, Jonathan M Weiss, James Mier, David Panka, David F McDermott, Paul M Sondel
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition...
December 2016: Cancer Immunology, Immunotherapy: CII
Suliman Y Alomar, Afrah Alkhuriji, Paul Trayhyrn, Abdulkarim Alhetheel, Abdullah Al-Jurayyan, Lamjed Mansour
Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women...
September 15, 2016: Immunogenetics
Camilla Stephens, Antonia Moreno-Casares, Miguel-Ángel López-Nevot, Miren García-Cortés, Inmaculada Medina-Cáliz, Hacibe Hallal, German Soriano, Eva Roman, Francisco Ruiz-Cabello, Manuel Romero-Gomez, M Isabel Lucena, Raúl J Andrade
Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown...
2016: Frontiers in Pharmacology
Paul J Norman, Jill A Hollenbach, Neda Nemat-Gorgani, Wesley M Marin, Steven J Norberg, Elham Ashouri, Jyothi Jayaraman, Emily E Wroblewski, John Trowsdale, Raja Rajalingam, Jorge R Oksenberg, Jacques Chiaroni, Lisbeth A Guethlein, James A Traherne, Mostafa Ronaghi, Peter Parham
The physiological functions of natural killer (NK) cells in human immunity and reproduction depend upon diverse interactions between killer cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands: HLA-A, HLA-B, and HLA-C. The genomic regions containing the KIR and HLA class I genes are unlinked, structurally complex, and highly polymorphic. They are also strongly associated with a wide spectrum of diseases, including infections, autoimmune disorders, cancers, and pregnancy disorders, as well as the efficacy of transplantation and other immunotherapies...
August 4, 2016: American Journal of Human Genetics
Danillo G Augusto
The polymorphism of killer cell immunoglobulin-like receptors (KIR) has been associated with several diseases, including infection, autoimmunity and cancer. KIR molecules are a family of receptors expressed on the surface of natural killer cells (NK), frontline defense of innate immunity against microorganisms and neoplastic cells. Some studies have shown conflicting results concerning the role that KIR polymorphism plays in tumor susceptibility, particularly in leukemia and lymphoma. Interestingly, the presence of HLA ligands is sometimes strongly associated with several types of cancer and apparently is not related with their interaction with KIR...
2016: Frontiers in Genetics
María V Martínez-Sánchez, Adela Periago, Isabel Legaz, Lourdes Gimeno, Anna Mrowiec, Natividad R Montes-Barqueros, José A Campillo, José M Bolarin, María V Bernardo, María R López-Álvarez, Consuelo González, María C García-Garay, Manuel Muro, Valentin Cabañas-Perianes, Jose L Fuster, Ana M García-Alonso, José M Moraleda, María R Álvarez-Lopez, Alfredo Minguela
Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1(-)L2(+)L3(-) genotypes (2...
April 2016: Oncoimmunology
Viktoria Varbanova, Elissaveta Naumova, Anastasiya Mihaylova
Natural killer (NK) cells are considered crucial for the elimination of emerging tumor cells. Effector NK-cell functions are controlled by interactions of inhibitory and activating killer-cell immunoglobulin-like receptors (KIRs) on NK cells with human leukocyte antigen (HLA) class I ligands on target cells. KIR and HLA are highly polymorphic genetic systems segregating independently, creating a great diversity in KIR/HLA gene profiles in different individuals. There is an increasing evidence supporting the relevance of KIR and HLA ligand gene background for the occurrence and outcome of certain cancers...
April 2016: Cancer Immunology, Immunotherapy: CII
Yaewon Yang, Okjae Lim, Tae Min Kim, Yong-Oon Ahn, Hana Choi, Hyejin Chung, Bokyung Min, Jung Hyun Her, Sung Yoo Cho, Bhumsuk Keam, Se-Hoon Lee, Dong-Wan Kim, Yu Kyeong Hwang, Dae Seog Heo
Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor-ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo-expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors...
March 2016: Cancer Immunology Research
Loredana Ruggeri, Elena Urbani, Pascale André, Antonella Mancusi, Antonella Tosti, Fabiana Topini, Mathieu Bléry, Lucia Animobono, François Romagné, Nicolai Wagtmann, Andrea Velardi
Natural killer cells are key cells of the innate immune system. Natural killer cell receptor repertoires are diversified by a stochastic expression of killer-cell-immunoglobulin-like receptors and lectin-like receptors such as NKG2 receptors. All individuals harbor a subset of natural killer cells expressing NKG2A, the inhibitory checkpoint receptor for HLA-E. Most neoplastic and normal hematopoietic cells express HLA-E, the inhibitory ligand of NKG2A. A novel anti-human NKG2A antibody induced tumor cell death, suggesting that the antibody could be useful in the treatment of cancers expressing HLA-E...
May 2016: Haematologica
Bo Yoon Chang, Seon Beom Kim, Mi Kyeong Lee, Hyun Park, Sung Yeon Kim
Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages...
2015: International Journal of Molecular Sciences
J Zhen, L He, Y Xu, J Zhao, Q Yu, H Zou, G Sun, Z Deng
KIR2DL2 and KIR2DL3 segregate as alleles of the same killer cell immunoglobulin-like receptor (KIR) gene locus. They have been associated with viral infectious diseases and certain cancers and their allelic information may help to better comprehend mechanisms. The allelic polymorphism of KIR2DL2/2DL3 has been shown to influence their binding specificity and affinity to the HLA-C1 ligands. The present study aims to investigate the distribution of the allelic polymorphism of KIR2DL2/2DL3 in a southern Chinese population using sequence-specific primer polymerase chain reaction (PCR-SSP) and PCR-sequence-based typing (SBT) at the entire coding sequence...
November 2015: Tissue Antigens
Suliman Y Al Omar, Lamjed Mansour, Javid Ahmed Dar, Saleh Alwasel, Afrah Alkhuriji, Maha Arafah, Omar Al Obeed, Stephen Christmas
AIMS: We performed an association study to evaluate the contribution of 16 killer cell immunoglobulin-like receptor (KIR) genotype polymorphisms and the HLA-C1 and -C2 ligands in the development of colorectal cancer (CRC) in Saudi Arabian patients. METHODS: A total of 52 patients with different stages of malignant CRC as well as 70 healthy Saudi controls were enrolled at the King Khalid University Hospital. RESULTS: Our results showed that the frequency of the activating mutations KIR2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 was significantly higher in CRC patients compared to controls...
November 2015: Genetic Testing and Molecular Biomarkers
Zhi-Xin Qiu, Ying Peng, Wei-Min Li
BACKGROUND: The immunoglobulin-like glycoprotein CD226 (DNAX accessory molecule-1) represents receptor-activating cytotoxic T lymphocyte and natural killer cells taking part in tumor surveillance, the pathogenesis of inflammation, and autoimmune disorders. The aim of the present study is to analyze the association between polymorphisms rs763361 and rs727088 in the CD226 gene and their impact on the pathogenesis of non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) were used to genotype the single nucleotide polymorphisms (SNPs) rs763361 and rs727088 of the CD226 gene in 302 NSCLC patients and 389 ethnicity matched healthy controls...
2015: Therapeutics and Clinical Risk Management
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