keyword
https://read.qxmd.com/read/37426355/early-trail-engagement-elicits-potent-multimodal-targeting-of-melanoma-by-cd34-progenitor-cell-derived-nk-cells
#21
JOURNAL ARTICLE
Amanda A van Vliet, Ella Peters, Denise Vodegel, Daniëlle Steenmans, Monica Raimo, Susan Gibbs, Tanja D de Gruijl, Adil D Duru, Jan Spanholtz, Anna-Maria Georgoudaki
Umbilical cord blood (UCB) CD34+ progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF, perforin and granzyme B levels. Importantly, intrinsic perforin and Granzyme B load predicts NK cell cytotoxic capacity. Exploring the mode of action revealed involvement of the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46 and most importantly of TRAIL...
July 21, 2023: IScience
https://read.qxmd.com/read/37359555/dnam-1-chimeric-receptor-engineered-nk-cells-a-new-frontier-for-car-nk-cell-based-immunotherapy
#22
JOURNAL ARTICLE
Loredana Cifaldi, Ombretta Melaiu, Roberto Giovannoni, Monica Benvenuto, Chiara Focaccetti, Daniela Nardozi, Giovanni Barillari, Roberto Bei
DNAM-1 is a major NK cell activating receptor and, together with NKG2D and NCRs, by binding specific ligands, strongly contributes to mediating the killing of tumor or virus-infected cells. DNAM-1 specifically recognizes PVR and Nectin-2 ligands that are expressed on some virus-infected cells and on a broad spectrum of tumor cells of both hematological and solid malignancies. So far, while NK cells engineered for different antigen chimeric receptors (CARs) or chimeric NKG2D receptor have been extensively tested in preclinical and clinical studies, the use of DNAM-1 chimeric receptor-engineered NK cells has been proposed only in our recent proof-of-concept study and deserves further development...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37333207/cd155-blockade-enhances-allogeneic-natural-killer-cell-mediated-antitumor-response-against-osteosarcoma
#23
Monica M Cho, Longzhen Song, Aicha E Quamine, Fernanda Szewc, Lei Shi, Amy K Erbe, Jonathan D Ebben, David P Turicek, Jillian M Kline, Emily O Lafeber, Madison F Phillips, Amanda S Ceas, Paul M Sondel, Christian M Capitini
BACKGROUND: Osteosarcoma (OS) patients that present with metastatic disease have a poor prognosis and no curative options. Allogeneic bone marrow transplant (alloBMT) is curative for hematologic malignancies through the graft-versus-tumor (GVT) effect, but to date has been ineffective for solid tumors like OS. CD155 is expressed on OS and interacts strongly with the inhibitory receptors TIGIT and CD96 but also binds to the activating receptor DNAM-1 on natural killer (NK) cells but has never been targeted after alloBMT...
June 9, 2023: bioRxiv
https://read.qxmd.com/read/37327114/allelic-variation-of-kir-and-hla-tunes-the-cytolytic-payload-and-determines-functional-hierarchy-of-nk-cell-repertoires
#24
JOURNAL ARTICLE
Camille Philippon, Sudan Alvaro Tao, Dennis Clement, Alvaro Haroun-Izquierdo, Katherine M Kichula, Herman Netskar, Ludwig Brandt, Vincent Yi Sheng Oei, Minoru Kanaya, Pilar M Lanuza, Marie Schaffer, Jodie P Goodridge, Amir Horowitz, Faming Zhu, Quirin Hammer, Ebba Sohlberg, Rakesh Kumar Majhi, Lise Kveberg, Björn Önfelt, Paul J Norman, Karl-Johan Malmberg
The functionality of natural killer (NK) cells is tuned during education and associated with remodeling of the lysosomal compartment. We hypothesized that genetic variation of KIR and HLA, which is known to influence the functional strength of NK cells, fine tunes the payload of effector molecules stored in secretory lysosomes. To address this possibility, we performed a high-resolution analysis of KIR and HLA-class I genes in 365 blood donors and linked genotypes to granzyme B loading and functional phenotypes...
June 16, 2023: Blood Advances
https://read.qxmd.com/read/37325585/tigit-based-immunotherapeutics-in-lung-cancer
#25
REVIEW
Akshay J Patel, Gary W Middleton
In this review, we explore the biology of the TIGIT checkpoint and its potential as a therapeutic target in lung cancer. We briefly review a highly selected set of clinical trials that have reported or are currently recruiting in non-small cell and small cell lung cancer, a disease transformed by the advent of PD-1/PD-L1 checkpoint blockade immunotherapy. We explore the murine data underlying TIGIT blockade and further explore the reliance of effective anti-TIGIT therapy on DNAM-1(CD226)-positive activated effector CD8+ T cells...
2023: Immunotherapy advances
https://read.qxmd.com/read/37322531/immune-profile-of-primary-and-recurrent-epithelial-ovarian-cancer-cases-indicates-immune-suppression-a-major-cause-of%C3%A2-progression-and-relapse-of-ovarian-cancer
#26
JOURNAL ARTICLE
Pavan Kumar, Samruddhi Ranmale, Sanket Mehta, Hemant Tongaonkar, Vainav Patel, Amit Kumar Singh, Jayanti Mania-Pramanik
BACKGROUND: Ovarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes...
June 15, 2023: Journal of Ovarian Research
https://read.qxmd.com/read/37303464/an-efficient-feeder-free-and-chemically-defined-expansion-strategy-for-highly-purified-natural-killer-cells-derived-from-human-cord-blood
#27
JOURNAL ARTICLE
Tsutomu Nakazawa, Ryosuke Maeoka, Takayuki Morimoto, Ryosuke Matsuda, Mitsutoshi Nakamura, Fumihiko Nishimura, Shuichi Yamada, Ichiro Nakagawa, Young-Soo Park, Toshihiro Ito, Hiroyuki Nakase, Takahiro Tsujimura
INTRODUCTION: Natural killer cells (NKCs) are immune cells that can attack cancer cells through the direct recognition of ligands without prior sensitization. Cord blood-derived NKCs (CBNKCs) represent a promising tool for allogenic NKC-based cancer immunotherapy. Efficient NKC expansion and decreased T cell inclusion are crucial for the success of allogeneic NKC-based immunotherapy without inducing graft-versus-host reactions. We previously established an efficient ex vivo expansion system consisting of highly purified-NKCs derived from human peripheral blood...
December 2023: Regenerative Therapy
https://read.qxmd.com/read/37287972/sars-cov-2-infection-impairs-nk-cell-functions-via-activation-of-the-llt1-cd161-axis
#28
JOURNAL ARTICLE
Marzena Lenart, Magdalena Górecka, Michal Bochenek, Emilia Barreto-Duran, Artur Szczepański, Adrianna Gałuszka-Bulaga, Natalia Mazur-Panasiuk, Kazimierz Węglarczyk, Andżelika Siwiec-Koźlik, Mariusz Korkosz, Paweł P Łabaj, Monika Baj-Krzyworzeka, Maciej Siedlar, Krzysztof Pyrc
INTRODUCTION: Natural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on the balance between their activating and inhibitory receptors. The immune dysregulation observed in COVID-19 patients was previously associated with downregulation of NK cell numbers and function, yet the mechanism of inhibition of NK cell functions and the interplay between infected cells and NK cells remain largely unknown. METHODS: In this study we show that SARS-CoV-2 infection of airway epithelial cells can directly influence NK cell phenotype and functions in the infection microenvironment...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37006249/three-distinct-mechanisms-underlying-human-%C3%AE-%C3%AE-t-cell-mediated-cytotoxicity-against-malignant-pleural-mesothelioma
#29
JOURNAL ARTICLE
Yasuhiro Umeyama, Hirokazu Taniguchi, Hiroshi Gyotoku, Hiroaki Senju, Hiromi Tomono, Shinnosuke Takemoto, Hiroyuki Yamaguchi, Mohammed S O Tagod, Masashi Iwasaki, Yoshimasa Tanaka, Hiroshi Mukae
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive thoracic tumor with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors exhibit a promising effect in some patients with unresectable MPM in clinical trials, the majority of MPM patients show only modest response rates to the currently available treatments. It is thus imperative to develop novel and innovative therapeutic modalities for MPM, including immune effector cell-based therapies...
2023: Frontiers in Immunology
https://read.qxmd.com/read/36985819/md-simulation-reveals-regulation-of-mechanical-force-and-extracellular-domain-2-on-binding-of-dnam-1-to-cd155
#30
JOURNAL ARTICLE
Liping Fang, Yang Zhao, Pei Guo, Ying Fang, Jianhua Wu
Two extracellular domains of the adhesive receptor DNAM-1 are involved in various cellular biological processes through binding to ligand CD155, usually under a mechano-microenvironment. The first extracellular domain (D1) plays a key role in recognition, but the function of the second extracellular domain (D2) and effects of force on the interaction of DNAM-1 with CD155 remain unclear. We herein studied the interaction of DNAM-1 with CD155 by performing steered molecular dynamics (MD) simulations, and observed the roles of tensile force and D2 on the affinity of DNAM-1 to CD155...
March 21, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/36979144/nectin-family-ligands-trigger-immune-effector-functions-in-health-and-autoimmunity
#31
REVIEW
Doryssa Hermans, Lisa van Beers, Bieke Broux
The superfamily of immunoglobulin cell-adhesion molecules (IgCAMs) is a well-known family of cell-adhesion molecules used for immune-cell extravasation and cell-cell interaction. Amongst others, this family includes DNAX accessory molecule 1 (DNAM-1/CD226), class-I-restricted T-cell-associated molecule (CRTAM/CD355), T-cell-activated increased late expression (Tactile/CD96), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), Nectins and Nectin-like molecules (Necls). Besides using these molecules to migrate towards inflammatory sites, their interactions within the immune system can support the immunological synapse with antigen-presenting cells or target cells for cytotoxicity, and trigger diverse effector functions...
March 15, 2023: Biology
https://read.qxmd.com/read/36966873/effect-of-mtor-inhibition-with-sirolimus-on-natural-killer-cell-reconstitution-in-allogeneic-stem-cell-transplantation
#32
JOURNAL ARTICLE
Alvaro Haroun-Izquierdo, Pilar M Lanuza, Aline Pfefferle, Herman Netskar, Eivind H Ask, Johan Törlén, Andreas Björklund, Ebba Sohlberg, Karl-Johan Malmberg
BACKGROUND: Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and is emerging as a promising component of graft-versus-host disease (GVHD) prophylaxis regimens in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Multiple studies have explored the clinical benefits of adding sirolimus to GVHD prophylaxis, however detailed immunological studies have not yet been carried out in this context. Mechanistically, mTOR is at the center of metabolic regulation in T- and NK cells and is critical for their differentiation to mature effector cells...
March 24, 2023: Transplantation and cellular therapy
https://read.qxmd.com/read/36851283/in-vitro-expansion-of-v%C3%AE-1-t-cells-from-cord-blood-by-using-artificial-antigen-presenting-cells-and-anti-cd3-antibody
#33
JOURNAL ARTICLE
Gaeun Hur, Haeyoun Choi, Yunkyeong Lee, Hyun-Jung Sohn, Su-Yeon Kim, Tai-Gyu Kim
γδ T cells have the potential for adoptive immunotherapy since they respond to bacteria, viruses, and tumors. However, these cells represent a small fraction of the peripheral T-cell pool and require activation and proliferation for clinical benefits. In cord blood, there are some γδ T cells, which exhibit a naïve phenotype, and mostly include Vδ1+ T cells. In this study, we investigated the effect of CD3 signaling on cord blood γδ T-cell proliferation using K562-based artificial antigen presenting cells expressing costimulatory molecules...
February 10, 2023: Vaccines
https://read.qxmd.com/read/36845105/the-co-inhibitory-receptor-tigit-regulates-nk-cell-function-and-is-upregulated-in-human-intrahepatic-cd56-bright-nk-cells
#34
JOURNAL ARTICLE
Annerose E Ziegler, Pia Fittje, Luisa M Müller, Annika E Ahrenstorf, Kerri Hagemann, Sven H Hagen, Leonard U Hess, Annika Niehrs, Tobias Poch, Gevitha Ravichandran, Sebastian M Löbl, Benedetta Padoan, Sébastien Brias, Jana Hennesen, Myrtille Richard, Laura Richert, Sven Peine, Karl J Oldhafer, Lutz Fischer, Christoph Schramm, Glòria Martrus, Madeleine J Bunders, Marcus Altfeld, Sebastian Lunemann
The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56bright NK cells in regulating tissue homeostasis remains incompletely understood. A targeted single-cell mRNA analysis revealed distinct transcriptional differences between matched human peripheral blood and intrahepatic CD56bright NK cells...
2023: Frontiers in Immunology
https://read.qxmd.com/read/36672396/pvrig-expression-is-an-independent-prognostic-factor-and-a-new-potential-target-for-immunotherapy-in-hepatocellular-carcinoma
#35
JOURNAL ARTICLE
David Jeremie Birnbaum, Maelle Picard, Quentin Da Costa, Thomas Delayre, Pascal Finetti, Olivier Cabaud, Emilie Agavnian, Bernadette De Rauglaudre, Emilie Denicolaï, François Bertucci, Emilie Mamessier
Hepatocellular carcinoma (HCC) is a frequent and deadly cancer in need of new treatments. Immunotherapy has shown promising results in several solid tumors. The TIGIT/DNAM-1 axis gathers targets for new immune checkpoint inhibitors (ICIs). Here, we aimed at highlighting the potential of this axis as a new therapeutic option for HCC. For this, we built a large transcriptomic database of 683 HCC samples, clinically annotated, and 319 normal liver tissues. We interrogated this database for the transcriptomic expression of each member of the TIGIT/DNAM-1 axis and tested their prognostic value for survival...
January 10, 2023: Cancers
https://read.qxmd.com/read/36585877/identification-of-the-cd16low-cd56low-cd38pos-natural-killer-cell-as-a-key-subset-in-patients-with-multiple-myeloma
#36
JOURNAL ARTICLE
Ting Chen, Zhenghong Yu
BACKGROUND: Natural killer (NK) cells are classified as innate immune cells which can directly recognize and kill tumor cells without antigen sensitization. NK cell-based adoptive immunotherapy for blood malignancies has attracted more attention in recent years. OBJECTIVE: To analyze different NK cell subsets in the peripheral blood and bone marrow (BM) of patients with multiple myeloma (MM). METHODS: Using flow cytometry we analyzed: (i) the distribution of distinct NK cell subpopulations (i...
December 2022: Iranian Journal of Immunology: IJI
https://read.qxmd.com/read/36585162/cytotoxicity-of-human-hepatic-intrasinusoidal-gamma-delta-t-cells-depends-on-phospho-antigen-and-nk-receptor-signaling
#37
JOURNAL ARTICLE
Yoorha Kang, Mina Han, Minsong Kim, Hyun Ju Hwang, Byung Chan Ahn, Eunyoung Tak, Gi-Won Song, Shin Hwang, Kyung-Nam Koh, Dong-Hwan Jung, Nayoung Kim
BACKGROUND/AIM: We previously showed that human hepatic intrasinusoidal (HI) natural killer (NK) T cells selectively eliminate hepatocellular carcinoma (HCC) cell lines. In this study, we investigated the underlying mechanisms on how HI γδ T cells, expanded with zoledronate, exhibit a superior cytotoxic effect on HI NK-resistant Huh7 HCC cells. MATERIALS AND METHODS: γδ T cells were obtained from living liver transplant donors or from peripheral blood mononuclear cells (PBMC) of healthy volunteers and were expanded in the presence of IL-2, IL-15, and zoledronate for 2 weeks...
January 2023: Anticancer Research
https://read.qxmd.com/read/36498937/preventing-surgery-induced-nk-cell-dysfunction-using-anti-tgf-%C3%AE-immunotherapeutics
#38
JOURNAL ARTICLE
Marisa Market, Gayashan Tennakoon, Marlena Scaffidi, David P Cook, Leonard Angka, Juliana Ng, Christiano Tanese de Souza, Michael A Kennedy, Barbara C Vanderhyden, Rebecca C Auer
Natural Killer (NK) cell cytotoxicity and interferon-gamma (IFNγ) production are profoundly suppressed postoperatively. This dysfunction is associated with increased morbidity and cancer recurrence. NK activity depends on the integration of activating and inhibitory signals, which may be modulated by transforming growth factor-beta (TGF-β). We hypothesized that impaired postoperative NK cell IFNγ production is due to altered signaling pathways caused by postoperative TGF-β. NK cell receptor expression, downstream phosphorylated targets, and IFNγ production were assessed using peripheral blood mononuclear cells (PBMCs) from patients undergoing cancer surgery...
November 23, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36497240/the-dual-blockade-of-the-tigit-and-pd-1-pd-l1-pathway-as-a-new-hope-for-ovarian-cancer-patients
#39
REVIEW
Anna Pawłowska, Wiktoria Skiba, Dorota Suszczyk, Weronika Kuryło, Joanna Jakubowicz-Gil, Roman Paduch, Iwona Wertel
The prognosis for ovarian cancer (OC) patients is poor and the five-year survival rate is only 47%. Immune checkpoints (ICPs) appear to be the potential targets in up-and-coming OC treatment. However, the response of OC patients to immunotherapy based on programmed cell death pathway (PD-1/PD-L1) inhibitors totals only 6-15%. The promising approach is a combined therapy, including other ICPs such as the T-cell immunoglobulin and ITIM domain/CD155/DNAX accessory molecule-1 (TIGIT/CD155/DNAM-1) axis. Preclinical studies in a murine model of colorectal cancer showed that the dual blockade of PD-1/PD-L1 and TIGIT led to remission in the whole studied group vs...
November 23, 2022: Cancers
https://read.qxmd.com/read/36480269/extracellular-cirp-induces-novel-nectin-2-cd112-neutrophils-to-promote-th1-differentiation-in-sepsis
#40
JOURNAL ARTICLE
Kensuke Murata, Atsushi Murao, Monowar Aziz, Ping Wang
Neutrophil heterogeneity represents different subtypes, states, phenotypes, and functionality of neutrophils implicated in sepsis pathobiology. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that promotes inflammation and alters neutrophil phenotype and function through TLR4. Nectin-2 or CD112 is an Ig-like superfamily member. CD112 serves as the ligand for DNAM-1 (CD226), which induces Th1 differentiation in naive CD4+ T cells. Th1 cells produce IFN-γ to fuel inflammation...
February 1, 2023: Journal of Immunology
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