Search Results (322)

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-γ (IFN-γ)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-γ-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-γ-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition. Full article

Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Type-I Interferon (IFN) is essential for antiviral immunity in both mice and humans; thus, we investigated whether LAT affects HSV-1 infectivity in the absence of IFN by infecting IFNαβR^−/− and wild-type control mice with HSV-1 McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. IFNαβR^−/− mice survived ocular infection with the LAT-plus virus, while no infected mice survived infection with the LAT-minus virus. Increased death in infected mice correlated with a higher expression in the neurovirulence γ34.5 gene but not with gB expression. To determine the region of LAT that contributed to higher mortality, IFNαβR^−/− mice were infected with recombinant viruses expressing the first 1.5 kb or the first 811bp region of 1.5 kb LAT. Similar to LAT-plus infected mice, IFNαβR^−/− mice infected with LAT1.5kb were protected from death, while infection with the LAT811bp virus was similar to that of LAT-minus, suggesting that increased pathogenicity in the absence of LAT depends on the second half of 1.5 kb LAT. To confirm the in vivo upregulation of γ34.5 expression in the absence of LAT, rabbit skin and Neuro2A cells were infected with LAT-plus, LAT-minus, LAT1.5kb, or LAT811bp viruses. γ34.5 expression was significantly higher in LAT-minus- and LAT811bp-infected rabbit skin cells and Neuro2A cells than in LAT-plus- and LAT1.5kb-infected cells, suggesting that sequences after the 811bp of LAT contribute to γ34.5 upregulation. However, except for γ34.5 expression, ICP0, ICP4, and gB expression were not affected by the absence of LAT or truncated forms of LAT. To confirm that higher γ34.5 expression contributes to higher mortality in the absence of LAT, we infected IFNαβR^−/− mice with a recombinant virus lacking LAT and γ34.5 expression, and, in contrast to LAT-minus, all infected mice survived. Our results suggest that LAT controls γ34.5 expression and that higher γ34.5 expression and mortality in infected mice are associated with the second half of 1.5 kb LAT. Full article

Interferon (IFN) signaling plays vital roles in host defense against viral infection. However, a variety of observations have been reported in the literature regarding the roles of IFN signaling in COVID-19. Thus, it would be important to reach a clearer picture regarding the activation or suppression of IFN signaling in COVID-19. In this work, regulation of marker genes for IFN signaling was examined in natural infection, viral challenge, and vaccination based on 13 public transcriptome datasets. Three subsets of interferon-stimulated genes (ISGs) were selected for detailed examination, including one set of marker genes for type I IFN signaling (ISGa) and two sets of marker genes for type II IFN signaling (IFN-γ signaling, GBPs for the GBP gene cluster, and HLAd for the HLA-D gene cluster). In natural infection, activation of ISGa and GBPs was accompanied by the suppression of HLAd in hospitalized patients. Suppression of GBPs was also observed in certain critical conditions. The scale of regulation was much greater for ISGa than that of GBPs and HLAd. In addition, the suppression of HLAd was correlated with disease severity, and it took much longer for HLAd to return to the level of healthy controls than that for ISGa and GBPs. Upon viral challenge, the activation of ISGa and GBPs was similar to that of natural infection, while the suppression of HLAd was not observed. Moreover, GBPs’ return to the pre-infection level was at a faster pace than that of ISGa. Upon COVID-19 vaccination, activation was observed for all of these three gene sets, and the scale of activation was comparable for ISGa and GBPs. Notably, it took a much shorter time for GBPs and ISGa to return to the level of healthy controls than that in COVID-19 infection. In addition, the baseline values and transient activation of these gene sets were also associated with subsequent vaccination response. The intricate balance of IFN signaling was demonstrated in mild breakthrough infection, where attenuated response was observed in people with prior vaccination compared to that in vaccine-naïve subjects. Overall, distinctive temporal profiles of IFN signaling were observed in natural infection, viral challenge, and vaccination. The features observed in this work may provide novel insights into the disease management and vaccine development. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung–brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using multiplex electrochemiluminescence and western blot. Differentially expressed genes (DEGs) were identified by RNA sequencing, and elastic net modeling was used to define exposure-predictive gene signatures. CBN exposure altered inflammatory biomarkers across tissues, with activation of nuclear factor kappa B (NF-κB) signaling. In the lung, gene set enrichment revealed activated pathways related to proliferation and inflammation, while epithelial–mesenchymal transition (EMT) and oxidative phosphorylation were suppressed. In the brain, EMT, inflammation, and senescence pathways were activated, while ribosomal function and oxidative metabolism were downregulated. Elastic net modeling identified a lung gene signature predictive of CBN exposure, including Kcnq3, Tgfbr1, and Tm4sf19. These findings demonstrate that inhalation of a surrogate burn pit mixture induces inflammatory and metabolic gene expression changes in both lung and brain tissues, supporting the utility of this animal model for understanding systemic effects of airborne military toxicants and for identifying potential biomarkers relevant to DRRD and Veteran health. Full article

The active form of vitamin D₃, 1,25(OH)₂D₃, exerts hierarchical control over gene expression, initially targeting transcription factors (TFs) that drive downstream responses. Here, we profile the transcriptional landscape of primary keratinocytes (HPEKp) and squamous cell carcinoma (SCC) cells in response to 1,25(OH)₂D₃, revealing a distinct shift in regulatory targets. While TFs accounted for 9.23% of differentially expressed genes (DEGs) in keratinocytes, this proportion dropped to 4.9% with prolonged exposure. In contrast, SCC cells displayed a five-fold reduction in TFs deregulation and a concurrent enrichment of long non-coding RNAs (lncRNAs), which comprised 22.25% of DEGs after 24 h treatment, with 81% upregulated. Integrative transcriptomic and in silico analyses showed that lncRNA induction was predominantly VDR-dependent, partially RXRA-dependent, and PDIA3-independent. Notably, 90% of deregulated lncRNAs were atypical for head and neck SCC. Several of these lncRNAs exhibit potential antitumor properties and may modulate SCC cell responsiveness to interferon-gamma (IFN-γ). In conclusion, these findings suggest that in SCC cells, the regulation of lncRNA expression—rather than transcription factor modulation—may represent a mechanism of the cellular response to 1,25(OH)₂D₃. Full article

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is a common form of esophageal cancer with a poor prognosis and limited treatment options. Epidermal growth factor receptor (EGFR), an overexpressed oncogenic gene in all ESCC patients, is an attractive target for developing therapies against ESCC. There is an extremely urgent need to develop immunotherapy tools targeting EGFR for the treatment of ESCC. Methods: In this study, we developed human Interleukin-21 (hIL-21)-armed, chimeric-antigen-receptor-modified T (CAR-T) cells targeting EGFR as a new therapeutic approach. The CAR contains a variable domain of the llama heavy chain of heavy-chain antibodies (VHHs), also known as nanobodies (Nbs), as a promising substitute for the commonly used single-chain variable fragment (ScFv) for CAR-T development. Results: We show that nanobody-derived, EGFR-targeting CAR-T cells specifically kill EGFR-positive esophageal cancer cells in vitro and in animal models. Human IL-21 expression in CAR-T cells further improved their expansion and antitumor ability and were observed to secrete more interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and Interleukin-2 (IL-2) when co-cultured with ESCC cell lines in vitro. More CD8⁺ CAR-T cells and CD3⁺CD8⁺CD45RO⁺CD62L⁺ central memory T cells were detected in CAR-T cells expressing hIL-21 cells. Notably, hIL-21-expressing CAR-T cells showed superior antitumor activity in vivo in a KYSE-150 xenograft mouse model. Conclusions: Our results show that hIL-21-armed, nanobody-derived, EGFR-specific CAR-T cell therapy is a highly promising option for treating ESCC patients. Full article

Natural killer (NK) cell adoptive immunotherapy is a promising therapeutic approach in which NK cells perform targeted lysis of tumor cells. Oncolytic viruses are also effective cancer therapeutic agents due to their ability to selectively target and kill tumor cells. Combination therapies that integrate NK cells and oncolytic viruses have been shown to enhance tumor killing compared to individual treatment strategies alone. Using in vitro expanded human NK cells (PM21-NK cells), we tested the relative ability of tumor cells infected with WT parainfluenza virus 5 (PIV5), which is a poor inducer of type 1 interferon (IFN-I), versus PIV5 P/V gene mutant, which is a strong inducer of IFN-I synthesis, to modulate NK cell activities. Both WT and P/V mutant viruses were capable of infecting PM21-NK cells and caused extensive cytopathic effects. Co-culturing of PM21-NK cells with virus-infected tumor cells resulted in spread of WT PIV5 to naïve NK cells, but NK cells were protected from spread of the P/V mutant virus by IFN-I induction. Direct treatment of PM21-NK cells with IFN-I or media from P/V-virus-infected tumor cells enhanced NK cell cytotoxicity, at least in part due to upregulation of the death ligand, TRAIL. IFN-I-treated PM21-NK cells also showed a decrease in IFN-γ secretion, a cytokine we have previously shown to reduce PM21-NK cell tumor killing. Our results highlight multiple mechanisms by which an IFN-I-inducing oncolytic virus can enhance NK-cell-mediated killing of target virus-infected and uninfected tumor cells. Full article

Background: The STING (Stimulator of Interferon Genes) pathway plays a vital role in the body’s innate immune defense system, primarily involved in DNA sensing and type I interferon production. While STING is well-established in various immune cells, its role in natural killer (NK) cells, particularly within the context of liver fibrosis, remains inadequately explored. Aim: The current study investigates the relationship between STING expression, NK cell activity, and insulin receptor (IR) signaling in patients with metabolic dysfunction-associated steatohepatitis (MASH). Methods: Peripheral NK cells were isolated from healthy controls and MASH patients with varying stages of liver fibrosis (early: F1/F2; advanced: F3/F4). The expressions of STING, IR, NK cell activation markers (CD107a, NKp46), and NK cell inhibitory markers (LAIR-1, Siglec-7) were assessed using flow cytometry. NK cell cytotoxicity against primary hepatic stellate cells (pHSCs) was evaluated through apoptosis assays. STING agonists (2′3′-cGAMP and DMXAA) were used to stimulate NK cells, and their effects on STING expression, NK cell activation, and cytotoxicity were measured. Additionally, the impact of insulin signaling on STING expression and NK cell function was examined. Results: Our results demonstrate that STING expression in NK cells correlates with disease severity in liver fibrosis. NK cells from MASH patients with advanced fibrosis (F3/F4) showed inhibited STING protein levels that were statistically comparable to healthy NK cells and accompanied by impaired cytotoxicity and decreased IFN-γ production. In contrast, NK cells from early fibrosis (F1/F2) exhibited higher STING expression and better functional activity. STING agonist treatment (2′3′-cGAMP) restored STING expression and enhanced NK cell activity across all fibrosis stages. Furthermore, insulin treatment and combined insulin and 2′3′-cGAMP treatment synergistically upregulated both IR and STING expressions, leading to improved NK cell function and increased cytotoxicity, particularly in advanced fibrosis. Conclusion: Our results highlight the potential of targeting STING and insulin signaling pathways as a therapeutic approach in restoring NK cell function and enhance immune surveillance in liver fibrosis. Full article

Diclofenac is an effective medication for pain and inflammation. However, its use has been linked to hepatitis. To gain insight into diclofenac’s ability to cause hepatitis, we investigated the regulation of major effectors of the immune system following daily treatment of minipigs at 3 and 15 mg/kg for 28 days. Histopathology evidenced lobular inflammation, and through a combination of immunogenomics and immunopathology, we detected marked innate and adaptive immune responses. We identified 109 significantly regulated genes linked to neutrophil, monocyte, Kupffer cell, and lymphocyte responses and 32 code for cytokine- and interferon-γ-signaling. In support of wound repair, immunopathology evidenced manifest upregulation of macrophage migration inhibitory factor and CD74. Furthermore, the strong expression of IgG and IgM underscored humoral immune responses. Diclofenac caused an activation of the complement system, especially the C1 inhibitor of the classical pathway and C3 with critical functions in liver regeneration. The marked expression of complement factor B and H of the alternate pathway modulated B-cell responses. Likely, the upregulation of factor H protected hepatocytes from injury by limiting complement-mediated damage of inflamed cells. Additionally, diclofenac treatment elicited marked hepatic expression of lysozyme and KLF6. The latter earmarks M1-polarized Kupffer cells. We observed an extraordinary induction of calprotectin/S100A9 and of the monocyte/macrophage CD163 scavenger receptor, and therefore, we detected innate immune sensing of damaged cells. Lastly, we noted an unprecedented induction of the acute phase reactant SAA1 and DEC-205, which recognize apoptotic and necrotic cells. Together, our results offer mechanistic insights into immune-mediated liver injury patterns following diclofenac treatment. Full article

Particulate matter (PM) is a major environmental pollutant implicated in various respiratory diseases. However, its impact on the upper respiratory tract, particularly the nasal and paranasal sinus mucosa, remains poorly understood. This study aimed to investigate the acute inflammatory effects of PM exposure on the sinonasal mucosa and evaluate the natural recovery process in a controlled rat model. Ten-week-old male Sprague Dawley rats were exposed to incense-derived PM in a custom-designed exposure chamber for 2 h daily for seven consecutive days. Rats were sacrificed at 3, 7, and 14 days post-exposure. Histopathologic changes were assessed using hematoxylin and eosin and Alcian blue staining, and mucosal gene expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-5 and MUC5AC was quantified using real-time reverse transcription polymerase chain reaction. PM exposure induced significant histological alterations, including epithelial thickening, inflammatory cell infiltration, and goblet cell hyperplasia, which peaked at 7 days post-exposure. Expression levels of TNF-α and IFN-γ were significantly elevated at 7 days compared to controls. The sinonasal mucosa in the 14-day post-exposure groups exhibited a remarkable decrease in goblet cell numbers, and IL-1β and TNF-α expression. Short-term exposure to high concentrations of PM resulted in acute inflammatory changes in the sinonasal mucosa of rats, including epithelial thickening and goblet cell hyperplasia. These changes were partially resolved after exposure ended, indicating that PM-induced sinonasal inflammation may be at least partially reversible. Full article

Cancer/testis antigen (CTA) gene products are expressed in most malignant tumours, while under normal conditions their expression is primarily restricted to testicular cells. In this study, we investigated the prophylactic application of a xenogeneic (ram-derived) testicular cell (TC) vaccine for cancer prevention in an experimental animal model. C57BL/6 mice were immunised three times with either xenogeneic (ram) or syngeneic (mouse) formaldehyde-fixed spermatogenic tissue-derived cells. Following vaccination, mice were implanted with live B16 melanoma or LLC carcinoma cells. Tumour-bearing mice were subsequently assessed for survival and immunological parameters indicative of anti-cancer immunity. Xenogeneic vaccination with TCs induced cross-reactive immune responses to both B16 melanoma and LLC carcinoma antigens (Ags), as determined by an MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Prophylactic vaccination with xenogeneic TCs (xTCs), but not syngeneic TCs (sTCs), significantly improved survival rates, with 30% of vaccinated mice surviving after LLC carcinoma implantation. The induced immunity was long-lasting as mice implanted with LLC carcinoma cells 3–6 months post-vaccination exhibited prolonged survival. Furthermore, lymphoid cells from surviving vaccinated mice were capable of adoptively transferring anti-cancer immunity to naïve animals, significantly increasing their survival rates upon subsequent LLC carcinoma cell implantation. Vaccinated mice bearing LLC tumours exhibited a reduction in regulatory CD4⁺CD25⁺Foxp3⁺ T cells in the spleen, with no effect observed in the central memory CD4⁺CD44⁺CD62L⁺ T-cell compartment. Moreover, vaccinated mice displayed increased interferon gamma (IFN-γ) levels in the blood, with no significant changes in interleukin-10 (IL-10) levels. Prophylactic vaccination with xenogeneic CTAs effectively induces long-term, stable anti-cancer immunity, demonstrating potential for future immunopreventive strategies. Full article