Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cordycepin Sensitizes Cholangiocarcinoma Cells to Be Killed by Natural Killer-92 (NK-92) Cells.

ABSTRACT: Immunotherapy harnessing immune functions is a promising strategy for cancer treatment. Tumor sensitization is one approach to enhance tumor cell susceptibility to immune cell cytotoxicity that can be used in combination with immunotherapy to achieve therapeutic efficiency. Cordycepin, a bioactive compound that can be extracted from some Cordyceps spp. has been reported to effectively inhibit tumor growth, however, the mechanism of its tumor sensitization activity that enhances immune cell cytotoxicity is unknown. In the present study, we investigated the potency of cordycepin to sensitize a lethal cancer, cholangiocarcinoma (CCA), to natural killer (NK) cells. Treatment with cordycepin prior to and during co-culturing with NK-92 cells significantly increased cell death of KKU-213A as compared to solitary cordycepin or NK treatment. Moreover, sensitization activity was also observed in the combination of NK-92 cells and Cordyceps militaris extract that contained cordycepin as a major component. The cordycepin treatment remarkably caused an increase in TRAIL receptor (DR4 and DR5) expression in KKU-213A, suggesting the possible involvement of TRAIL signaling in KKU-213A sensitization to NK-92 cells. In conclusion, this is the first report on the sensitization activity of cordycepin on CCA cells to NK cytotoxicity, which supports that cordycepin can be further developed as an alternate immunomodulating agent.

SUBMITTER: Panwong S

PROVIDER: S-EPMC8512070 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Natural Killer Cells for Immunotherapy - Advantages of the NK-92 Cell Line over Blood NK Cells.

Project description:Natural killer (NK) cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells from a patient's blood since they represent only 10% of the lymphocytes and are often dysfunctional. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T cells to prevent graft-versus-host reactions. Cytotoxic cell lines have been established from patients with clonal NK-cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. Except for the NK-92 cell line, though, none of the other six known NK cell lines has consistently and reproducibly shown high antitumor cytotoxicity. Only NK-92 cells can easily be genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through antibody-dependent cellular cytotoxicity. NK-92 is also the only cell line product that has been infused into patients with advanced cancer with clinical benefit and minimal side effects.

| S-EPMC4789404 | biostudies-literature

Genistein Sensitizes Human Cholangiocarcinoma Cell Lines to Be Susceptible to Natural Killer Cells.

Project description:Cholangiocarcinoma (CCA) is a lethal bile duct cancer, which has poor treatment outcomes due to its high resistance to chemotherapy and cancer recurrence. Activation of aberrant anti-apoptotic signaling pathway has been reported to be a mechanism of chemoresistance and immune escape of CCA. Therefore, reversal of anti-apoptotic signaling pathway represents a feasible approach to potentiate effective treatments, especially for CCA with high chemoresistance. In this study, we demonstrated the effects of genistein on reactivation of apoptosis cascade and increase the susceptibility of CCA cells to natural killer (NK-92) cells. Genistein at 50 and 100 µM significantly activated extrinsic apoptotic pathway in CCA cells (KKU055, KKU100, and KKU213A), which was evident by reduction of procaspase-8 and -3 expression. Pretreatment of CCA cells with genistein at 50 µM, but not NK-92 cells, significantly increased NK-92 cell killing ability over the untreated control, suggesting the ability of genistein to sensitize CCA cells. Interestingly, genistein treatment could greatly lower the expression of cFLIP, an anti-apoptotic protein involved in the immune escape pathway, in addition to upregulation of death receptors, Fas- and TRAIL-receptors, in CCA cells, which might be the underlying molecular mechanism of genistein to sensitize CCA to be susceptible to NK-92 cells. Taken together, this finding revealed the benefit of genistein as a sensitizer to enhance the efficiency of NK cell immunotherapy for CCA.

| S-EPMC9330512 | biostudies-literature

Natural Killer Cells and Current Applications of Chimeric Antigen Receptor-Modified NK-92 Cells in Tumor Immunotherapy.

Project description:Natural killer (NK) cells are innate immune cells that can be activated rapidly to target abnormal and virus-infected cells without prior sensitization. With significant advancements in cell biology technologies, many NK cell lines have been established. Among these cell lines, NK-92 cells are not only the most widely used but have also been approved for clinical applications. Additionally, chimeric antigen receptor-modified NK-92 cells (CAR-NK-92 cells) have shown strong antitumor effects. In this review, we summarize established human NK cell lines and their biological characteristics, and highlight the applications of NK-92 cells and CAR-NK-92 cells in tumor immunotherapy.

| S-EPMC6358726 | biostudies-literature

Natural Killer Cell Line NK-92-Mediated Damage of Medically Important Fungi.

Project description:Invasive fungal disease (IFD) in hematopoietic stem cell transplantation is associated with high morbidity and mortality. As the antifungal host response determines risk and outcome of IFD, there is growing interest in adoptive immunotherapy using T cells or natural killer (NK) cells. Although the NK-92 cell line has been tested as anticancer therapy in clinical trials, data on the antifungal activity of NK-92 cells are lacking. Here, we show that the NK-92 cell line exhibits considerable fungal damage on all medically important fungi tested, such as different species of Aspergillus, Candida, mucormycetes, and Fusarium. The extent of fungal damage differs across various species of mucormycetes and Fusarium, whereas it is comparable across different species of Aspergillus and Candida. Interferon (IFN)-? levels in the supernatant were lower when NK-92 cells are co-incubated with Aspergillus fumigatus, Candida albicans, or Rhizopus arrhizus compared to the levels when NK-92 cells are incubated alone. Different to primary human NK cells, no increase of perforin levels in the supernatant was observed when the fungi were added to NK-92 cells. Our in vitro data demonstrated that the NK-92 cell line could be a feasible tool for antifungal immunotherapy, but data of animal models are warranted prior to clinical trials.

| S-EPMC7922546 | biostudies-literature

Proliferation of Highly Cytotoxic Human Natural Killer Cells by OX40L Armed NK-92 With Secretory Neoleukin-2/15 for Cancer Immunotherapy.

Project description:Adoptive natural killer (NK) cell transfer has been demonstrated to be a promising immunotherapy approach against malignancies, but requires the administration of sufficient activated cells for treatment effectiveness. However, the paucity of clinical-grade to support the for large-scale cell expansion limits its feasibility. Here we developed a feeder-based NK cell expansion approach that utilizes OX40L armed NK-92 cell with secreting neoleukin-2/15 (Neo-2/15), a hyper-stable mimetic with a high affinity to IL-2Rβγ. The novel feeder cells (NK92-Neo2/15-OX40L) induced the expansion of NK cells with a 2180-fold expansion (median; 5 donors; range, 1767 to 2719) after 21 days of co-culture without added cytokines. These cells were highly cytotoxic against Raji cells and against several solid tumors in vivo. Mechanistically, NK92-Neo2/15-OX40L induced OX40 and OX40L expression on expanded NK cells and promoted the OX40-OX40L positive feedback loop, thus boosting NK cell function. Our data provided a novel NK cell expansion mechanism and insights into OX40-OX40L axis regulation of NK cell expansion.

| S-EPMC8083131 | biostudies-literature

Non-Genetically Improving the Natural Cytotoxicity of Natural Killer (NK) Cells.

Project description:The innate lymphocyte lineage natural killer (NK) is now the target of multiple clinical applications, although none has received an agreement from any regulatory agency yet. Transplant of naïve NK cells has not proven efficient enough in the vast majority of clinical trials. Hence, new protocols wish to improve their medical use by producing them from stem cells and/or modifying them by genetic engineering. These techniques have given interesting results but these improvements often hide that natural killers are mainly that: natural. We discuss here different ways to take advantage of NK physiology to improve their clinical activity without the need of additional modifications except for in vitro activation and expansion and allograft in patients. Some of these tactics include combination with monoclonal antibodies (mAb), drugs that change metabolism and engraftment of specific NK subsets with particular activity. Finally, we propose to use specific NK cell subsets found in certain patients that show increase activity against a specific disease, including the use of NK cells derived from patients.

| S-EPMC6970430 | biostudies-literature

Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy.

Project description:Natural killer (NK) cells are potent innate immune system effector lymphocytes armed with multiple mechanisms for killing cancer cells. Given the dynamic roles of NK cells in tumor surveillance, they are fast becoming a next-generation tool for adoptive immunotherapy. Many strategies are being employed to increase their number and improve their ability to overcome cancer resistance and the immunosuppressive tumor microenvironment. These include the use of cytokines and synthetic compounds to bolster propagation and killing capacity, targeting immune-function checkpoints, addition of chimeric antigen receptors (CARs) to provide cancer specificity and genetic ablation of inhibitory molecules. The next generation of NK cell products will ideally be readily available as an "off-the-shelf" product and stem cell derived to enable potentially unlimited supply. However, several considerations regarding NK cell source, genetic modification and scale up first need addressing. Understanding NK cell biology and interaction within specific tumor contexts will help identify necessary NK cell modifications and relevant choice of NK cell source. Further enhancement of manufacturing processes will allow for off-the-shelf NK cell immunotherapies to become key components of multifaceted therapeutic strategies for cancer.

| S-EPMC8146003 | biostudies-literature

Activating natural killer (NK) cytotoxicity of canine CD5-CD21- cells requires low surface CD5 density NK cells.

Project description:Natural killer (NK) cells play a crucial role in regulating immune functions. Few studies have characterized canine NK cells. We previously demonstrated that canine peripheral blood lymphocytes (PBLs) with a low surface CD5 density (CD5lo) are considered a critical NK population. Natural killer cells in most mammals do not express T-cell markers, but canine CD5lo cells express surface molecules, such as CD3 T-cell receptors. These features make canines unique models for the study of comparative immunology in NK cells. In this study, we discovered that CD5lo and CD21 double-negative (CD5lo-ne/CD2-) cells were originally low in NK cytotoxicity and their NK cytotoxicity was highly activated when co-cultured with CD5lo NK cells. The cytotoxicity was not activated when co-cultured with other cell types, such as high surface CD5 density (CD5hi) cells. The CD5lo-negative (CD5lo-ne) population comprises CD5- and CD5hi cells. CD5-cells were low in NK cytotoxicity initially or after culturing with interleukin-2 (IL-2) without CD5lo cells; however, the addition of CD5lo cells in a similar medium markedly enhanced the NK activity. By contrast, CD5hi cells were always NK inactive, irrespective of them being cultured with CD5lo cells or not. We further verified that only the CD5-CD21- cells, which were separated from CD5-CD21+ cells in the entire CD5- population, showed activated NK activity through CD5lo cell induction. This study is the first to reveal that canine NK cells enhanced NK-inert cells to become NK-cytotoxic cells. Additionally, it is concluded that in beagles, except for CD5lo cells, CD5-CD21- cells show NK activity.

| S-EPMC6056148 | biostudies-literature

Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells.

Project description:Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001.

| S-EPMC3975579 | biostudies-literature