Modulation Of Immune Cells Research Articles

Single-cell omics and machine learning integration to develop a polyamine metabolism-based risk score model in breast cancer patients

BackgroundBreast cancer remains the leading malignant neoplasm among women globally, posing significant challenges in terms of treatment and prognostic evaluation. The metabolic pathway of polyamines is crucial in breast cancer progression, with a strong association to the increased capabilities of tumor cells for proliferation, invasion, and metastasis.MethodsWe used a multi-omics approach combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to study polyamine metabolism. Data from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression identified 286 differentially expressed genes linked to polyamine pathways in breast cancer. These genes were analyzed using univariate COX and machine learning algorithms to develop a prognostic scoring algorithm. Single-cell RNA sequencing validated the model by examining gene expression heterogeneity at the cellular level.ResultsOur single-cell analyses revealed distinct subpopulations with different expressions of genes related to polyamine metabolism, highlighting the heterogeneity of the tumor microenvironment. The SuperPC model (a constructed risk score) demonstrated high accuracy when predicting patient outcomes. The immune profiling and functional enrichment analyses revealed that the genes identified play a crucial role in cell cycle control and immune modulation. Single-cell validation confirmed that polyamine metabolism genes were present in specific cell clusters. This highlights their potential as therapeutic targets.ConclusionsThis study integrates single cell omics with machine-learning to develop a robust scoring model for breast cancer based on polyamine metabolic pathways. Our findings offer new insights into tumor heterogeneity, and a novel framework to personalize prognosis. Single-cell technologies are being used in this context to enhance our understanding of the complex molecular terrain of breast cancer and support more effective clinical management.

Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, we aim to prioritize agents in this category of therapeutics for glioblastoma.

CRISPR–Cas9 delivery strategies for the modulation of immune and non-immune cells

CRISPR–Cas9 delivery strategies for the modulation of immune and non-immune cells

A proteomics perspective on 2 years of high-intensity training in horses: a pilot study

The human plasma proteome is rather well studied, but not that of other species, including horses. The aims of this study were to (1), explore differences in plasma proteomic profile of young elite harness trotters kept under standardised conditions and subjected to two different training programmes for 2 years and (2) explore changes in proteomic profile over time during the training period. From September at age 1.5 year to March at age 2 years, 16 Standardbred horses were exposed to the same training programme. In March, high-intensity training was introduced and the horses were divided into two training groups (High and Low). Blood samples were collected at rest in December as 1.5-year-olds, July as 2-year-olds, December as 2.5-year-olds and December as 3.5-year-olds. Untargeted proteomics was performed and a hypothesis-generating approach was used in statistical analysis (t-tests). At the age of 2.5 years, the level of serotransferrin was higher in the High group (P = 0.01) and at least at one sampling occasion, proteins associated with fat metabolism, oxidant/antioxidant processes, cardiovascular responses, bone formation and inflammation were lower in High group compared to Low (P < 0.05). Analyses of changes over time revealed that levels of proteins involved in energy metabolism, red cell metabolism, circulation, oxidant/antioxidant activity, bone formation, inflammation, immune modulation and cellular and vascular damage changed (P < 0.05). The results indicate that proteomics analysis of blood plasma could be a viable tool for evaluation of exercise adaptations, performance and for health monitoring, with several potential biomarkers identified in this study.

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes

BackgroundDuctal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.ResultsWe identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.ConclusionsWe identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

The Metformin Immunoregulatory Actions in Tumor Suppression and Normal Tissues Protection.

The immune system is the key player in a wide range of responses in normal tissues and tumors to anticancer therapy. Inflammatory and fibrotic responses in normal tissues are the main limitations of chemotherapy, radiotherapy, and also some newer anticancer drugs such as immune checkpoint inhibitors (ICIs). Immune system responses within solid tumors including anti-tumor and tumor-promoting responses can suppress or help tumor growth. Thus, modulation of immune cells and their secretions such as cytokines, growth factors and epigenetic modulators, pro-apoptosis molecules, and some other molecules can be suggested to alleviate side effects in normal tissues and drug-resistance mechanisms in the tumor. Metformin as an anti-diabetes drug has shown intriguing properties such as anti-inflammation, anti-fibrosis, and anticancer effects. Some investigations have uncovered that metformin can ameliorate radiation/chemotherapy toxicity in normal cells and tissues through the modulation of several targets in cells and tissues. These effects of metformin may ameliorate severe inflammatory responses and fibrosis after exposure to ionizing radiation or following treatment with highly toxic chemotherapy drugs. Metformin can suppress the activity of immunosuppressive cells in the tumor through the phosphorylation of AMP-activated protein kinase (AMPK). In addition, metformin may stimulate antigen presentation and maturation of anticancer immune cells, which lead to the induction of anticancer immunity in the tumor. This review aims to explain the detailed mechanisms of normal tissue sparing and tumor suppression during cancer therapy using adjuvant metformin with an emphasis on immune system responses.

Oncogenic miRNAs dependent photothermal-immunotherapy enhanced by on-demand manipulation of immunosuppressive microenvironment using engineered gold nanoparticles for effective treatment of primary and metastatic tumor

Although photothermal-immunotherapy has emerged as a promising strategy to treat malignant tumor, unexpected thermal damage, continuous tumor migration and immunosuppressive microenvironment still limit its application. To improve the therapeutic efficacy, two types of engineered gold nanoparticles (SNAs@CCM and SNA2@CCM-Man) were fabricated. The SNAs@CCM are cancer cell membrane (CCM, tumor targeting agent) coated spherical nucleic acids (SNAs, miR-21 catcher and photothermal agent). The SNAs contained two types (SNA1 and SNA2), which are gold nanoparticles grafted with the first half and second half of anti-miR-21 oligonucleotide, respectively. The SNA2@CCM-Man are CCM coated SNA2 (miR-21 catcher) in which the CCM was functionalized by mannose (Man, macrophage targeting agent). These nanoparticles were expected to not only perform miR-21 dependent photothermal-immunotherapy in tumor cells to precisely damage primary tumor and activate the anti-tumor immune response against metastatic tumor, but also restrain the miR-21 expression in tumor-associated M2-type macrophages to promote their polarization to tumor-suppressed M1-type macrophages for on-demand manipulation of immunosuppressive microenvironment avoiding immune escape. After injection, the SNAs@CCM and SNA2@CCM-Man would respectively internalize by tumor cells and M2-type macrophages via homologous targeting of cancer cell membranes and receptor-ligand interactions of mannose. Upon entry into tumor cells, the SNAs specifically hybridized with the over-expressed miR-21 in these cells, thereby silencing the oncogenic miR-21 and leading to significant intracellular aggregation of SNAs. These aggregated SNAs not only served as miR-21 catcher, but performed a strong absorption in the near-infrared region acting as in situ photothermal agents. Under NIR irradiation, these photothermal agents enable highly selective photothermal-immunotherapy, inducing the immunogenic death of primary tumors and subsequent anti-tumor immune responses via the maturation of dendritic cells (DCs) and activation of T cells. Moreover, the miR-21 plunder process also effectively inhibited the migration of tumor cells to further enhance the therapeutic efficacy. Simultaneously, the similar miR-21 capture process mediated by SNA2 in M2 macrophages continuously induced macrophage polarization towards the anti-tumor M1 type, which was able to reverse the immunosuppressive microenvironment in tumor tissue to avoid immune escape and enhance immunotherapy. Both in vivo and in vitro experiments demonstrated that our nanoparticles could inhibit the primary tumor and its metastasis through miR-21-dependent photothermal immune activation and directional polarization of macrophages, providing a promising strategy for on-demand synchronous modulation of tumor cells and immune cells in tumor tissues for better malignant tumor therapy.

Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its involvement in immune homeostasis and cancer biology with an emphasis on multiple myeloma (MM) pathophysiology, highlighting its complex and context-dependent dual functions as a pro- and anti-tumorigenic molecule and its potential implications for therapy in MM patients.

Lipid nanoparticle-mediated RNA delivery for immune cell modulation.

Lipid nanoparticles (LNPs) have emerged as the preeminent nonviral drug delivery vehicles for nucleic acid therapeutics, as exemplified by their usage in the mRNA COVID-19 vaccines. As a safe and highly modular delivery platform, LNPs are attractive for a wide range of applications. In addition to vaccines, LNPs are being utilized as platforms for other immunoengineering efforts, especially as cancer immunotherapies by modulating immune cells and their functionality via nucleic acid delivery. In this review, we focus on the methods and applications of LNP-based immunotherapy in five cell types: T cells, NK cells, macrophages, stem cells, and dendritic cells. Each of these cell types has wide-reaching applications in immunotherapy but comes with unique challenges and delivery barriers. By combining knowledge of immunology and nanotechnology, LNPs can be developed for improved immune cell targeting and transfection, ultimately working toward novel clinical therapeutics.

The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury.

This review explores the complex challenges and advancements in the treatment of traumatic brain injury (TBI) and spinal cord injury (SCI). Traumatic injuries to the central nervous system (CNS) trigger intricate pathophysiological responses, frequently leading to profound and enduring disabilities. This article delves into the dual phases of injury-primary impacts and the subsequent secondary biochemical cascades-that worsen initial damage. Conventional treatments have traditionally prioritized immediate stabilization, surgical interventions, and supportive medical care to manage both the primary and secondary damage associated with central nervous system injuries. We explore current surgical and medical management strategies, emphasizing the crucial role of rehabilitation and the promising potential of stem cell therapies and immune modulation. Advances in stem cell therapy, gene editing, and neuroprosthetics are revolutionizing treatment approaches, providing opportunities not just for recovery but also for the regeneration of impaired neural tissues. This review aims to emphasize emerging therapeutic strategies that hold promise for enhancing outcomes and improving the quality of life for affected individuals worldwide.

Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues.

Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (H2O2) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including the promotion of cell survival pathways and immune cell modulation in the tumor microenvironment. H2O2 is a reactive oxygen species (ROS) crucial in cellular homeostasis and signaling (at concentrations maintained under nM levels), with increased steady-state levels in tumors relative to their normal tissue counterparts. Increased steady-state levels of H2O2 in tumor cells, make them vulnerable to oxidative stress and ultimately, cell death. Recently, H2O2-producing therapies-namely, pharmacological ascorbate and superoxide dismutase mimetics-have emerged as compelling complementary treatment strategies in cancer. Both pharmacological ascorbate and superoxide dismutase mimetics can generate excess H2O2 to overwhelm the impaired H2O2 removal capacity of cancer cells. This review presents an overview of H2O2 metabolism in the physiological and malignant states, in addition to discussing the anti-tumor and normal tissue-sparing mechanism(s) of, and clinical evidence for, two H2O2-based therapies, pharmacological ascorbate and superoxide dismutase mimetics.

Microbiota and Recurrent Pregnancy Loss (RPL); More than a Simple Connection.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown that the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local pro-inflammatory Th1 and Th17 subpopulations and a decrease in local Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response, increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are required to ascertain the benefit of microbiota modulation in RPL.

Bufalin Suppresses Head and Neck Cancer Development by Modulating Immune Responses and Targeting the β-Catenin Signaling Pathway.

Bufalin, a cardiotonic steroid derived from the Chinese toad (Bufo gargarizans), has demonstrated potent anticancer properties across various cancer types, positioning it as a promising therapeutic candidate. However, comprehensive mechanistic studies specific to head and neck cancers have been lacking. Our study aimed to bridge this gap by investigating bufalin's mechanisms of action in head and neck cancer cells. Using several methods, such as Western blotting, immunofluorescence, and flow cytometry, we observed bufalin's dose-dependent reduction in cell viability, disruption of cell membrane integrity, and inhibition of colony formation in both HPV-positive and HPV-negative cell lines. Bufalin induces apoptosis through the modulation of apoptosis-related proteins, mitochondrial function, and reactive oxygen species production. It also arrests the cell cycle at the G2/M phase and attenuates cell migration while affecting epithelial-mesenchymal transition markers and targeting pivotal signaling pathways, including Wnt/β-catenin, EGFR, and NF-κB. Additionally, bufalin exerted immunomodulatory effects by polarizing macrophages toward the M1 phenotype, bolstering antitumor immune responses. These findings underscore bufalin's potential as a multifaceted therapeutic agent against head and neck cancers, targeting essential pathways involved in proliferation, apoptosis, cell cycle regulation, metastasis, and immune modulation. Further research is warranted to validate these mechanisms and optimize bufalin's clinical application.

Osteointegration of Ti Bone Implants: A Study on How Surface Parameters Control the Foreign Body Response.

The integration of titanium (Ti)-based implants with bone is limited, resulting in implant failure. This lack of osteointegration is due to the foreign body response (FBR) that occurs after the implantation of biodevices. The process begins with protein adsorption, which is governed by implant surface properties, e.g., chemistry, charge, wettability, and/or topography. The distribution and composition of the protein layer in turn influence the recruitment, differentiation, and modulation of immune and bone cells. The subsequent events that occur at the bone-material interface will ultimately determine whether the implant is encapsulated or will integrate with bone. Despite the numerous studies evaluating the influence of surface properties in the various stages of the FBR, the factors that affect tissue-material interactions are often studied in isolation or in small correlations due to the technical challenges involved in assessing them in vitro or in vivo. Consequently, the influence of protein conformation on the Ti bone implant surface design remains an unresolved research question. The objective of this review is to comprehensively evaluate the existing literature on the effect of surface parameters of Ti and its alloys in the stages of FBR, with a particular focus on protein adsorption and osteoimmunomodulation. This evaluation aims to systematically describe these effects on bone formation.

Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity.

Insect bite hypersensitivity (IBH) is the most frequent skin allergy of horses and is highly debilitating, especially in the chronic phase. IBH is caused by IgE-mediated hypersensitivity reactions to culicoides midge bites and an imbalanced immune response that reduces the welfare of affected horses. In the present study, we investigated the pathological mechanisms of IBH, aiming to understand the immune cell modulation in acute allergic skin lesions of IBH horses with the goal of finding possible biomarkers for a diagnostic approach to monitor treatment success. By qPCR, we quantified the gene expression of cytokines, chemokines, and immune receptors in skin punch biopsies of IBH with different severity levels and healthy horses simultaneously in tandem with the analysis of immune cell counts in the blood. Our data show an increase in blood eosinophils, monocytes, and basophils with a concomitant, significant increase in associated cytokine, chemokine, and immune cell receptor mRNA expression levels in the lesional skin of IBH horses. Moreover, IL-5Ra, CCR5, IFN-γ, and IL-31Ra were strongly associated with IBH severity, while IL-31 and IL-33 were rather associated with a milder form of IBH. In addition, our data show a strong correlation of basophil cell count in blood with IL-31Ra, IL-5, IL-5Ra, IFN-γ, HRH2, HRH4, CCR3, CCR5, IL-12b, IL-10, IL-1β, and CCL26 mRNA expression in skin punch biopsies of IBH horses. In summary, several cytokines and chemokines have been found to be associated with disease severity, hence contributing to IBH pathology. These molecules can be used as potential biomarkers to monitor the onset and progression of the disease or even to evaluate and monitor the efficacy of new therapeutic treatments for IBH skin allergy. To our knowledge, this is the first study that investigated immune cells together with a large set of genes related to their biological function, including correlation to disease severity, in a large cohort of healthy and IBH horses.

Effect of ultrasound-mediated blood-spinal cord barrier opening on survival and motor function in females in an amyotrophic lateral sclerosis mouse model

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.Cg-Tg(SOD1∗G93A)1Gur/J). The BSCB was disrupted using a 1MHz ultrasound transducer coupled to the spinal cord, with and without injection of insulin-like growth factor 1 (IGF1), a neurotrophic factor that has previously shown efficacy in ALS models. Results in wild-type (WT) animals demonstrated that the BSCB can be safely disrupted and IGF1 concentrations significantly enhanced after a single session of transient BSCB disruption (176±32μg/g vs. 0.16±0.008μg/g, p<0.0001). Five repeated weekly US sessions performed in female ALS mice demonstrated a survival advantage in mice treated with IGF1 and US (US IGF1) compared to treatment with IGF1 alone (176 vs. 166 days, p=0.0038). Surprisingly, this survival advantage was also present in mice treated with US alone vs. untreated mice (178.5 vs. 166.5 days, p=0.0061). Muscle strength did not show difference among the groups. Analysis of glial cell immunoreactivity and microglial transcriptome showing reduced cell proliferation pathways, in addition to lymphocyte infiltration, suggested that the beneficial effect of US or US IGF1 could act through immune cell modulation. These results show the first step towards a possible beneficial impact of transient BSCB opening for ALS therapy and suggest implication of immune cells. Fondation pour la Recherche Médicale (FRM). Investissements d'avenirANR-10-IAIHU-06, Société Française de Neurochirurgie (SFNC), Fond d'étude et de Recherche du Corps Medical (FERCM), Aide à la Recherche des Maladies du Cerveau (ARMC), SLA Fondation Recherche (SLAFR), French Ministry for High Education and Research (MENR), Carthera, Laboratoire de Recherche en Technologies Chirurgicales Avancées (LRTCA).

Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study.

The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs. Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren's syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality. Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including "CD25++ CD8+ T cell % CD8+ T cell" (mediation proportion: 6.2%) and "CD3 on activated CD4 regulatory T cell" (5.4%). Additionally, "CD127 on granulocyte" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05). This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.

Sweat exosomes: A new cutting edge nanomedicine in cancer treatment

AbstractExosomes can be defined as extracellular vesicles, of size ranging from 30 to 150 nm, secreted from almost all kinds of cells and can also be obtained from the body fluids. Exosomes have different components depending on the type of cell from which they originate. Exosomes are capable of transporting various molecules such as proteins, nucleic acids, chemical compounds and metabolites. Experiments show that exosomes can perform important functions in cell growth, migration, differentiation, neuronal signalling, immune cell modulation. Exosomes can also be used in cancer therapy, as they can be key players in intercellular communication and signalling. Experiments have also demonstrated that exosomes are chief players in viral persistence and dissemination. The reasons why application of exosomes in targeted therapy is gaining significance are their ability to initiate cellular responses, high tolerance levels in host cells and high efficiency in penetrating other cells. Exosomes can be used both as therapeutic agents and escorts of drugs. Even though numerous studies have been performed in search of better anticancer therapies, most of them have come to a halt due to the failure in achieving a therapy best in all parameters. However, both in vitro and in vivo application of exosomes in diagnosis and therapy of tumours are prospective and has a future.

Sulforaphane-mediated immune regulation through inhibition of NF-kB and MAPK signaling pathways in human dendritic cells

Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis and combating against pathogens. These processes involve complex signaling pathways, notably the Nuclear Factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways, which play crucial roles. Sulforaphane (SFN), a nutraceutic, has emerged as a potential regulator of NF-κB and MAPK signaling pathways, exhibiting anti-inflammatory properties. However, limited knowledge exists regarding SFN’s effects on immune cell modulation. This study aimed to assess the immunomodulatory capacity of SFN pretreatment in human dendritic cells (DCs), followed by exposure to a chronic inflammatory environment induced by lipopolysaccharide. SFN pretreatment was found to inhibit the NF-κB and MAPK signaling pathways, resulting in phenotypic changes in DCs characterized by a slight reduction in the expression of surface markers, as well as a decrease of TNF-α/IL-10 ratio. Additionally, SFN pretreatment enhanced the proliferation of Treg-cells and promoted the production of IL-10 by B-cells before exposure to the chronic inflammatory environment. Furthermore, these changes in DCs were found to be influenced by the inhibition of NF-κB and MAPK pathways (specifically p38 MAPK and JNK), suggesting that these pathways may play a role in the regulation of the differentiation of adaptive immune responses (proliferation of T- and IL-10-producing regulatory-cells), prior to SFN pretreatment. Our findings suggest that SFN pretreatment may induce a regulatory response by inhibiting NF-κB and MAPK signaling pathways in an inflammatory environment. SFN could be considered a promising strategy for utilizing functional foods to protect against inflammation and develop immunoregulatory interventions.

From bench to bedside: the past, present and future of IL-21 immunotherapy.

As immunotherapy gains momentum as a promising approach for treating several types of cancer, IL-21 has emerged as the latest discovery within the γ chain cytokine family, known for its decisive effects on innate and adaptive immunity and immunopathology. Through the modulation of immune cells, IL-21 has demonstrated significant anti-tumor effects in preclinical studies. The potential of IL-21 in cancer treatment has been explored in phase I and II clinical trials, where it has been utilized both as monotherapy and in combination with other drug agents. Further investigation, alongside larger studies, is necessary before final evaluation and application of IL-21 as immunotherapy. This review aims to summarize these pre-clinical and clinical studies and to discuss the possible future directions of IL-21 immunotherapy development. Such a study may be helpful to accelerate the process of clinical application for IL21 immunotherapy.