scholarly journals Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation

2006 ◽  
Vol 38 (5) ◽  
pp. 474-484 ◽  
Author(s):  
Joo-Young Kim ◽  
Young-Ok Son ◽  
Soon-Won Park ◽  
Jae-Ho Bae ◽  
Joo Seop Chung ◽  
...  
Keyword(s):  
Heat Shock ◽  
Ionizing Radiation ◽  
Tumor Cells ◽  
Nk Cell ◽  
Nkg2d Ligands

scholarly journals Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection

2005 ◽  
Vol 202 (11) ◽  
pp. 1477-1482 ◽  
Author(s):  
John M. Routes ◽  
Sharon Ryan ◽  
Kristin Morris ◽  
Rayna Takaki ◽  
Adelheid Cerwenka ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nk Cell ◽  
Tumor Rejection ◽  
Mouse Tumor ◽  
Mutant Form ◽  
Nkg2d Ligand ◽  
Adenovirus Serotype ◽  
Nkg2d Ligands ◽  
Serotype 5

The expression of the Adenovirus serotype 5 (Ad5) E1A oncogene sensitizes tumor cells to natural killer (NK) cell–mediated killing and tumor rejection in vivo. These effects are dependent on the ability of E1A to bind the transcriptional coadaptor protein p300. To test the hypothesis that E1A up-regulates ligands recognized by the NKG2D-activating receptor, we stably transfected the highly tumorigenic mouse fibrosarcoma cell line MCA-205 with Ad5-E1A or a mutant form of E1A that does not interact with p300 (E1A-Δp300). Ad5-E1A, but not E1A-Δp300, up-regulated the expression of the NKG2D ligand retinoic acid early inducible (RAE)-1, but not murine ULBP-like transcript 1, another NKG2D ligand, in four independently derived MCA-205 transfectants. The up-regulation of RAE-1 by E1A targeted MCA-205 tumor cells to lysis by NK cells, resulting in NKG2D-dependent tumor rejection in vivo. Moreover, the up-regulation of NKG2D ligands by E1A was not limited to mouse tumor cells, as E1A also increased the expression of NKG2D ligands on primary baby mouse kidney cells, human MB435S breast cancer cells, and human H4 fibrosarcoma cells.

Abstract 3652: Surface expression and shedding of NKG2D ligands by (metastasizing) tumor cells is altered by platelets leading to impaired NK cell immunosurveillance

2014 ◽  
Author(s):  
Stefanie Raab ◽  
Korbinian Nepomuk Kropp ◽  
Alexander Steinle ◽  
Gerd Klein ◽  
Hans-Georg Kopp ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nk Cell ◽  
Surface Expression ◽  
Nkg2d Ligands

scholarly journals Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells

2017 ◽  
Vol 7 (2) ◽  
pp. e1364827 ◽  
Author(s):  
Stefanie Maurer ◽  
Korbinian Nepomuk Kropp ◽  
Gerd Klein ◽  
Alexander Steinle ◽  
Sebastian P. Haen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Nkg2d Ligands

scholarly journals The Heat Shock Protein HSP70 Promotes Mouse NK Cell Activity against Tumors That Express Inducible NKG2D Ligands

2007 ◽  
Vol 179 (8) ◽  
pp. 5523-5533 ◽  
Author(s):  
Leslie Elsner ◽  
Vijayakumar Muppala ◽  
Mathias Gehrmann ◽  
Jingky Lozano ◽  
Dörthe Malzahn ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Nkg2d Ligands ◽  
Heat Shock Protein Hsp70

Quercetin Enhances Susceptibility to NK Cell-mediated Lysis of Tumor Cells Through Induction of NKG2D Ligands and Suppression of HSP70

2010 ◽  
Vol 33 (4) ◽  
pp. 391-401 ◽  
Author(s):  
Jae-Ho Bae ◽  
Joo-Young Kim ◽  
Mi-Ju Kim ◽  
Sung-Ho Chang ◽  
You-Soo Park ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nk Cell ◽  
Nkg2d Ligands

scholarly journals Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1102
Author(s):  
Alexander E. Kabakov ◽  
Anna O. Yakimova
Keyword(s):  
Heat Shock ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Liver Tumors ◽  
Oxygen Deficiency ◽  
Transarterial Embolization ◽  
Antiangiogenic Therapy ◽  
Adaptation To Hypoxia ◽  
Mesenchymal Transition

Within aggressive malignancies, there usually are the “hypoxic zones”—poorly vascularized regions where tumor cells undergo oxygen deficiency through inadequate blood supply. Besides, hypoxia may arise in tumors as a result of antiangiogenic therapy or transarterial embolization. Adapting to hypoxia, tumor cells acquire a hypoxia-resistant phenotype with the characteristic alterations in signaling, gene expression and metabolism. Both the lack of oxygen by itself and the hypoxia-responsive phenotypic modulations render tumor cells more radioresistant, so that hypoxic tumors are a serious challenge for radiotherapy. An understanding of causes of the radioresistance of hypoxic tumors would help to develop novel ways for overcoming this challenge. Molecular targets for and various approaches to radiosensitizing hypoxic tumors are considered in the present review. It is here analyzed how the hypoxia-induced cellular responses involving hypoxia-inducible factor-1, heat shock transcription factor 1, heat shock proteins, glucose-regulated proteins, epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial–mesenchymal transition and exosome generation contribute to the radioresistance of hypoxic tumors or may be inhibited for attenuating this radioresistance. The pretreatments with a multitarget inhibition of the cancer cell adaptation to hypoxia seem to be a promising approach to sensitizing hypoxic carcinomas, gliomas, lymphomas, sarcomas to radiotherapy and, also, liver tumors to radioembolization.

scholarly journals Cytokine-Induced Memory-Like NK Cells with High Reactivity against Acute Leukemia Blasts and Solid Tumor Cells Suitable for Adoptive Immunotherapy Approaches

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1577
Author(s):  
Matteo Tanzi ◽  
Michela Consonni ◽  
Michela Falco ◽  
Federica Ferulli ◽  
Enrica Montini ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Lymphoid Leukemia ◽  
Hematopoietic Stem ◽  
Solid Malignancies

The limited efficacy of Natural Killer (NK) cell-based immunotherapy results in part from the suboptimal expansion and persistence of the infused cells. Recent reports suggest that the generation of NK cells with memory-like properties upon in vitro activation with defined cytokines might be an effective way of ensuring long-lasting NK cell function in vivo. Here, we demonstrate that activation with IL-12, IL-15 and IL-18 followed by a one-week culture with optimal doses of Interleukin (IL-2) and IL-15 generates substantial numbers of memory-like NK cells able to persist for at least three weeks when injected into NOD scid gamma (NSG) mice. This approach induces haploidentical donor-derived memory-like NK cells that are highly lytic against patients’ myeloid or lymphoid leukemia blasts, independent of the presence of alloreactive cell populations in the donor and with negligible reactivity against patients’ non-malignant cells. Memory-like NK cells able to lyse autologous tumor cells can also be generated from patients with solid malignancies. The anti-tumor activity of allogenic and autologous memory-like NK cells is significantly greater than that displayed by NK cells stimulated overnight with IL-2, supporting their potential therapeutic value both in patients affected by high-risk acute leukemia after haploidentical hematopoietic stem cell transplantation and in patients with advanced solid malignancies.

scholarly journals Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 525
Author(s):  
Kwang-Soo Kim ◽  
Dong-Hwan Kim ◽  
Dong-Hyun Kim
Keyword(s):  
Clinical Trials ◽  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Therapeutic Efficacy ◽  
Nk Cell ◽  
Cell Cancer ◽  
Immune Surveillance ◽  
Cytolytic Activity ◽  
Contact Frequency

Among various immunotherapies, natural killer (NK) cell cancer immunotherapy using adoptive transfer of NK cells takes a unique position by targeting tumor cells that evade the host immune surveillance. As the first-line innate effector cell, it has been revealed that NK cells have distinct mechanisms to both eliminate cancer cells directly and amplify the anticancer immune system. Over the last 40 years, NK cell cancer immunotherapy has shown encouraging reports in pre-clinic and clinic settings. In total, 288 clinical trials are investigating various NK cell immunotherapies to treat hematologic and solid malignancies in 2021. However, the clinical outcomes are unsatisfying, with remained challenges. The major limitation is attributed to the immune-suppressive tumor microenvironment (TME), low activity of NK cells, inadequate homing of NK cells, and limited contact frequency of NK cells with tumor cells. Innovative strategies to promote the cytolytic activity, durable persistence, activation, and tumor-infiltration of NK cells are required to advance NK cell cancer immunotherapy. As maturing nanotechnology and nanomedicine for clinical applications, there is a greater opportunity to augment NK cell therapeutic efficacy for the treatment of cancers. Active molecules/cytokine delivery, imaging, and physicochemical properties of nanoparticles are well equipped to overcome the challenges of NK cell cancer immunotherapy. Here, we discuss recent clinical trials of NK cell cancer immunotherapy, NK cell cancer immunotherapy challenges, and advances of nanoparticle-mediated NK cell therapeutic efficacy augmentation.

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