Metallic Nanoparticles: Their Potential Role in Breast Cancer Immunotherapy via Trained Immunity Provocation.

Owing to drawbacks in the current common cancer therapies including surgery, chemotherapy and radiotherapy, the development of more reliable, low toxic, cost-effective and specific approaches such as immunotherapy is crucial. Breast cancer is among the leading causes of morbidity and mortality with a developed anticancer resistance. Accordingly, we attempted to uncover the efficacy of metallic nanoparticles (MNPs)-based breast cancer immunotherapy emphasizing trained immunity provocation or innate immunity adaptation. Due to the immunosuppressive nature of the tumor microenvironment (TME) and the poor infiltration of immune cells, the potentiation of an immune response or direct combat is a goal employing NPs as a burgeoning field. During the recent decades, the adaptation of the innate immunity responses against infectious diseases and cancer has been recognized. Although the data is in a scarcity with regard to a trained immunity function in breast cancer cells' elimination, this study introduced the potential of this arm of immunity adaptation using MNPs.

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

Leukocyte Reduction Filters Are Reliable and Economic Source for Natural Killer Cell Preparation.

Background: An issue that hinders researchers' access to Natural Killer (NK) cells is their low proportion in peripheral blood leukocytes. This issue is currently addressed by methods involving a series of differentiation and expansions that are time-consuming and expensive. Objective: We have investigated whether the used leukocyte reduction filters, a by-product in the blood transfusion practice that currently is considered waste, can be utilized as a source of the NK cells. Methods: Following the blood donation of 46 donors based on the Iranian Blood Transfusion Organization's protocols, a sample of peripheral blood of each donor and the leukocyte reduction filter used in their donation procedure have been obtained. The entrapped cells were flushed back from the leukocyte reduction filters. Both groups of samples were analyzed using an automatic hematological analyzer. NK cell isolation was done by the MACS negative selection method. The samples have been comparatively analyzed utilizing flow cytometry data of NK cells' subpopulation compositions, viability, degranulation patterns, and cytotoxic capacity against the K562 cell line. Results: Every major leukocyte population was abundant in the samples extracted from the used leukocyte reduction filters. The NK cells extracted from leukocyte reduction filters did not show any statistically meaningful differences (P<0.5) from peripheral blood samples in terms of subpopulation composition, viability, degranulation potency, and cytotoxic capacity. Conclusion: Used leukocyte reduction filters can be considered an economic, easy to obtain, and robust source of abundant research-grade NK cells.

Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.

Owing to non-responsiveness of a high number of patients to the common melanoma therapies, seeking novel approaches seem as an unmet requirement. Chimeric antigen receptor (CAR) T cells were initially employed against recurrent or refractory B cell malignancies. However, advanced stages or pretreated patients have insufficient T cells (lymphopenia) amount for collection and clinical application. Additionally, this process is time-consuming and logistically cumbersome. Another limitation of this approach is toxicity and cytokine release syndrome (CRS) progress and neurotoxicity syndrome (NS). Natural killer (NK) cells are a versatile component of the innate immunity and have several advantages over T cells in the application for therapies such as availability, unique biological features, safety profile, cost effectiveness and higher tissue residence. Additionally, CAR NK cells do not develop Graft-versus-host disease (GvHD) and are independent of host HLA genotype. Notably, the NK cells number and activity is affected in the tumor microenvironment (TME), paving the way for developing novel approaches by enhancing their maturation and functionality. The CAR NK cells short lifespan is a double edge sword declining toxicity and reducing their persistence. Bispecific and Trispecific Killer Cell Engagers (BiKE and Trike, respectively) are emerging and promising immunotherapies for efficient antibody dependent cell cytotoxicity (ADCC). CAR NK cells have some limitations in terms of expanding and transducing NK cells from donors to achieve clinical response. Clinical trials are in scarcity regarding the CAR NK cell-based cancer therapies. The CAR NK cells short life span following irradiation before infusion limits their efficiency inhibiting their in vivo expansion. The CAR NK cells efficacy enhancement in terms of lifespan TME preparation and stability is a goal for melanoma treatment. Combination therapies using CAR NK cells and chemotherapy can also overcome therapy limitations.

Memory and CAR-NK cell-based novel approaches for HIV vaccination and eradication.

Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV-infected cells. These cells identify and eliminate virus-infected cells in a multilateral manner, such as ligand stress, antibody-dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV-infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long-term maintenance of these HIV-reactive NK cells. CAR-NK (chimeric antigen receptor-natural killer) cells-based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR-T (chimeric antigen receptor-T) cells. Recent development of induced pluripotent stem cell (iPSC)-derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR-NK cell-based therapies. Therefore, memory and CAR-NK cells-based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.