Enhancement of Adjuvant Functions of Natural Killer T Cells Using Nanovector Delivery Systems: Application in Anticancer Immune Therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Ghinnagow R
PROVIDER: S-EPMC5529346 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Conventional natural killer (NK)-based anticancer immunotherapy has a limitation in that a culture period of approximately 2 weeks is required to increase the number and activity of NK cells. In addition, the anticancer activity of NK cells is closely associated with their mitochondrial function. In this study, we aimed to investigate whether the NK-anticancer activity increased after transferring allogeneic mitochondria into NK cells. Using this method, NK cells with enhanced anticancer activity can be produced without in vitro culture and can be used for anticancer treatment.
2024-01-22 | GSE224187 | GEO
Project description:Dendritic cells (DCs) and NK cells play a crucial role in the first phase of host defense against infections. Group B Streptococcus (GBS) and Streptococcus suis are encapsulated streptococci causing severe systemic inflammation, leading to septicemia and meningitis. Yet, the involvement of NK cells in the innate immune response to encapsulated bacterial infection is poorly characterized. Here, it was observed that these two streptococcal species rapidly induce the release of IFN-γ and that NK cells are the major cell type responsible for this production during the acute phase of the infection. Albeit S. suis capacity to activate NK cells was lower than that of GBS, these cells partially contribute to S. suis systemic infection; mainly through amplification of the inflammatory loop. In contrast, such a role was not observed during GBS systemic infection. IFN-γ release by NK cells required the presence of DCs, which in turn had a synergistic effect on DC cytokine production. These responses were mainly mediated by direct DC-NK cell contact and partially dependent on soluble factors. Though IL-12 and LFA-1 were shown to be critical in S. suis-mediated activation of the DC-NK cell crosstalk, different or redundant molecular pathways modulate DC-NK interactions during GBS infection. The bacterial capsular polysaccharides also differently modulated NK cell activation. Together, these results demonstrated a role of NK cells in the innate immune response against encapsulated streptococcal infections; yet the molecular pathways governing NK activation seem to differ upon the pathogen and should not be generalized when studying bacterial infections.
| S-EPMC5489694 | biostudies-literature
Project description:Recent studies have demonstrated that radiotherapy is able to induce anti-tumor immune responses in addition to mediating direct cytotoxic effects. Cancer-associated fibroblasts (CAFs) are central constituents of the tumor stroma and participate actively in tumor immunoregulation. However, the capacity of CAFs to influence immune responses in the context of radiotherapy is still poorly understood. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on natural killer (NK) cells. CAFs were isolated from freshly resected non-small cell lung cancer tissues, while NK cells were prepared from peripheral blood of healthy donors. Functional assays to study NK cell immune activation included proliferation rates, expression of cell surface markers, secretion of immunomodulators, cytotoxic assays, as well as production of intracellular activation markers such as perforin and granzyme B. Our data show that CAFs inhibit NK cell activation by reducing their proliferation rates, the cytotoxic capacity, the extent of degranulation, and the surface expression of stimulatory receptors, while concomitantly enhancing surface expression of inhibitory receptors. Radiation delivered as single high-dose or in fractioned regimens did not reverse the immunosuppressive features exerted by CAFs over NK cells in vitro, despite triggering enhanced surface expression of several checkpoint ligands on irradiated CAFs. In summary, CAFs mediate noticeable immune inhibitory effects on cytokine-activated NK cells during co-culture in a donor-independent manner. However, ionizing radiation does not interfere with the CAF-mediated immunosuppressive effects.
| S-EPMC7874190 | biostudies-literature
Project description:Enhancement of the anticancer ability of natural killer cells through allogeneic mitochondrial transfer
| PRJNA930031 | ENA
Project description:BackgroundThe immune system plays a pivotal role in the initiation, evolution, invasion and metastasis of cancer. Therapeutics aiming at modulating or boosting anticancer immune responses have experienced immense advances during the past decades, for example, anti-PD-1/PD-L1 monoclonal antibodies.Main bodyConcomitant with advancements in the understanding of novel mechanisms of action, conventional or emerging drugs bearing the potential to be repurposed for enhancing anticancer immunity have been identified. Meanwhile, ongoing advances in drug delivery systems enable us to utilise novel therapeutic strategies and impart drugs with fresh modes of action in tumour immunology.ConclusionHerein, we systemically review these kinds of drugs and delivery systems that can unleash the anticancer response through various aspects, including immune recognition, activation, infiltration and tumour killing. We also discuss the current caveats and future directions of these emerging strategies.
| S-EPMC10320767 | biostudies-literature
Project description:The MYC oncogene drives T- and B- lymphoid malignancies, including Burkitt's lymphoma (BL) and Acute Lymphoblastic Leukemia (ALL). Here, we demonstrate a systemic reduction in natural killer (NK) cell numbers in SRα-tTA/Tet-O-MYCON mice bearing MYC-driven T-lymphomas. Residual mNK cells in spleens of MYCON T-lymphoma-bearing mice exhibit perturbations in the terminal NK effector differentiation pathway. Lymphoma-intrinsic MYC arrests NK maturation by transcriptionally repressing STAT1/2 and secretion of Type I Interferons (IFNs). Treating T-lymphoma-bearing mice with Type I IFN improves survival by rescuing NK cell maturation. Adoptive transfer of mature NK cells is sufficient to delay both T-lymphoma growth and recurrence post MYC inactivation. In MYC-driven BL patients, low expression of both STAT1 and STAT2 correlates significantly with the absence of activated NK cells and predicts unfavorable clinical outcomes. Our studies thus provide a rationale for developing NK cell-based therapies to effectively treat MYC-driven lymphomas in the future.
| S-EPMC7275060 | biostudies-literature
Project description:Natural killer (NK) cells are innate lymphocytes that directly kill tumor and pathogen-infected cells upon activation by cytokines and NK cell receptors (NKRs) without previous sensitization. It is known that cell metabolism affects the differentiation and effector functions of immune cells. For instance, interleukin-2 and interleukin-15 treatment increases glycolysis and oxidative phosphorylation (OXPHOS) in NK cells to support their effector functions. However, little is known about the metabolic reprogramming of human NK cells upon their activation by NKRs. In this study, we investigated the metabolism of NK cells stimulated via NKRs. We found that NK cells upregulated glycolysis and OXPHOS in response to anti-CD16 antibody or NKG2D ligand engagement. Inhibition of either glycolysis or OXPHOS impaired NK cell production of interferon-?. Interestingly, inhibition of glycolysis but not OXPHOS decreased NK cell killing and dampened NK cell degranulation and Fas ligand expression, suggesting that glycolysis is more critical for NKR-activated cell cytotoxicity. Thus, our study provides insight into understanding the metabolic requirements underlying different effector functions of human NK cells.
| S-EPMC7045049 | biostudies-literature
Project description:Pancreatic cancer, a highly malignant disease, is characterized by rapid progression and early metastasis. Although the integrative treatment of pancreatic cancer has made great progress, the prognosis of patients with advanced pancreatic cancer remains extremely poor. In recent years, with the advancements in tumor immunology, immunotherapy has become a promising remedy for pancreatic cancer. Natural killer (NK) cells are the key lymphocytes in the innate immune system. NK cell function does not require antigen pre-sensitization and is not major histocompatibility complex restricted. By targeting tumors or virus-infected cells, the cells play a key role in immune surveillance. Although several questions about NK cells in pancreatic cancer still need to be further studied, there are extensive theories supporting the clinical application prospects of NK cell immunotherapy in pancreatic cancer. Since very few studies have evaluated the role of NK cells in pancreatic cancer, this review provides a comprehensive update of the role of NK cells in pancreatic cancer immunotherapy.
| S-EPMC8299011 | biostudies-literature
Project description:In an adaptive immune response, naive T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000-fold in the liver after infection. After a contraction phase, Ly49H-positive NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing 'memory' NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.
| S-EPMC2674434 | biostudies-literature
Project description:Mucosal surfaces are protected from infection by both structural and sentinel cells, such as mast cells. The mast cell's role in antiviral responses is poorly understood; however, they selectively recruit natural killer (NK) cells following infection. Here, the ability of virus-infected mast cells to enhance NK cell functions was examined. Cord blood-derived human mast cells infected with reovirus (Reo-CBMC) and subsequent mast cell products were used for the stimulation of human NK cells. NK cells upregulated the CD69 molecule and cytotoxicity-related genes, and demonstrated increased cytotoxic activity in response to Reo-CBMC soluble products. NK cell interferon (IFN)-γ production was also promoted in the presence of interleukin (IL)-18. In vivo, SCID mice injected with Reo-CBMC in a subcutaneous Matrigel model, could recruit and activate murine NK cells, a property not shared by normal human fibroblasts. Soluble products of Reo-CBMC included IL-10, TNF, type I and type III IFNs. Blockade of the type I IFN receptor abrogated NK cell activation. Furthermore, reovirus-infected mast cells expressed multiple IFN-α subtypes not observed in reovirus-infected fibroblasts or epithelial cells. Our data define an important mast cell IFN response, not shared by structural cells, and a subsequent novel mast cell-NK cell immune axis in human antiviral host defense.
| S-EPMC6738812 | biostudies-other