Immune Competence Research Articles

Research Progress on Anti-Tumor Mechanism of Tannins in Traditional Chinese Medicine

By reviewing the literature on the efficacy of tannins in traditional Chinese medicine in the last decade or so, we have classified the anti-tumor mechanism of tannins in conjunction with the latest mechanism exploration in the field of oncology. Tannins, a class of multi-phenolic compounds widely present in the diet, have been studied by scholars worldwide in recent years because of their relatively outstanding pharmacological activities. The mechanisms of anti-tumor action of tannins can be summarized as follows: the arrest of the cell cycle, arrest of tumor migration, enhancement of immune competence, induction of apoptosis, and antioxidant effects.

Effects of the In ovo Administration of the 6/85 Mycoplasma gallisepticum Vaccine on Layer Chicken Embryo Hatchability and Early Posthatch Performance

In ovo administration as a possible alternative method of 6/85 MG vaccination was assessed. After 18 days of incubation (doi), the eggs were administered a particular dosage of a live attenuated 6/85 MG vaccine in either the air cell (AC) or amnion (AM). The treatments included non-injected eggs and eggs injected into the AC or AM with diluent alone as controls. Treatments also included eggs injected with diluent, which contained 1.73 × 102, or 1.73 × 104 CFU of 6/85 MG. Hatchability of viable injected eggs (HI) and residual embryonic mortality were determined at 22 doi. At hatch and at three weeks posthatch, one hatched chick per treatment replicate was bled and swabbed for the detection of 6/85 MG in the choanal cleft using PCR, serum plate agglutination (SPA), and ELISA methods. The results show that AC in ovo injection of 6/85 MG had no negative impacts on HI or on the live performance of pullets, but that it failed to provide adequate protection (p ≤ 0.0001) in hatchlings or three-week-old pullets. The 1.73 × 104 6/85 MG CFU dosage injected into the AM decreased the hatchability of injected eggs containing viable embryos (HI; p = 0.009) and was associated with a significant increase in late dead mortality (p = 0.001). Hatchling and three-week-old chick mortalities (p = 0.008) were significantly greater in the 1.73 × 104 CFU-AM treatment group in comparison with the other treatment groups. In addition, the 1.73 and 1.73 × 102 6/85 MG-AM treatments had no negative effects on the hatching process or on posthatch growth, and the 1.73 × 102 6/85 MG-AM treatment was more effective in the protection of pullets against MG (p ≤ 0.0001) as compared with the low dosage and non-injected treatment groups. Further research is needed to examine the influence of the 6/85 MG in ovo vaccine on layer immune competence.

Effect of selection for growth rate on the rabbit (Oryctolagus cuniculus) immune system and its response after experimental Staphylococcus aureus infection.

The aim of the work was to evaluate if genetic selection for daily gain may affect the immune system. Two experiments were performed. The first one involved 80 rabbit females and their first two litters to explore the effect of selection on the ability of animals to maintain immune competence. Two generations from a line selected for average daily gain (ADG) were evaluated (VR19 generation 19th, n = 43; VR37 generation 37th, n = 37). In females, the effect of selection and its interaction with physiological state were not significant for any trait. In litters, the selection criterion increased the granulocyte to lymphocyte ratio. The second experiment involved 73 19-week-old females (VR19, n = 39; VR37, n = 34) to explore the effect of genetic selection on immune response after S. aureus infection. The VR37 rabbit females had lower counts for total lymphocytes, CD5+, CD4+, CD8+, CD25+, monocytes, the CD4+/CD8+ ratio and platelets than those of VR19 (-14, -21, -25, -15, -33, -18, -11 and -11%, respectively; P < 0.05). VR37 had less erythema (-8.4 percentage points; P < 0.05), fewer nodules (-6.5 percentage points; P < 0.05) and a smaller nodule size (-0.65 cm3 on 7day post-inoculation; P < 0.05) compared to VR19. Our study suggests that genetic selection for average daily gain does not negatively affect the maintenance of a competent immune system or the ability to establish immune response. It seems that such selection may improve the response to S. aureus infections.

Maternal treatment with pegbovigrastim influences growth performance and immune-metabolic status of calves during the pre-weaning period

This study aimed to investigate the immune-metabolic status and growth performance of Simmental calves born from cows subjected to pegbovigrastim administration 7 days before calving. Eight calves born from cows subjected to pegbovigrastim administration (PEG group) and 9 calves born from untreated cows (CTR group) were used. Growth measurements and blood samples were collected from birth to 60 d of age. The PEG group had lower body weight from 28 up to 60 d of age (P < 0.01), lower heart girth (P < 0.05), lower weekly and total average daily gain values (P < 0.05) than the CTR group throughout the monitoring period. A decrease in milk replacer (MR) intake was observed in the PEG group compared with the CTR group around 20–28 d of age (P < 0.01). The PEG group had lower values of γ-glutamyl transferase (GGT) at d 1 of age (P < 0.05), Zn at 21 and 28 d of age (P < 0.05), hemoglobin, MCH and MCHC at 54 and 60 d of age (P < 0.01), and higher urea concentration at 21 and 28 d of age (P < 0.05) compared with the CTR group. Lower values of retinol (P < 0.05), tocopherol (P < 0.01), mean myeloperoxidase index (P < 0.05) and higher total reactive oxygen metabolites (P < 0.05) and myeloperoxidase (P < 0.05) were also detected in the PEG group. In light of the results gathered in the current study, it can be speculated that activation of the cow's immune system by pegbovigrastim could have influenced the immune competence, growth performance as well as the balance between oxidant and antioxidant indices of the newborn calf.

Vertebrate–arthropod communication dictates tick development and pathogen transmission

Cross-species communication drives the coordination of diverse biological processes in complex systems. Rana et al. discovered that Ixodes scapularis, the tick vector of Lyme disease, produces a receptor that binds host interferon-gamma (IFNγ) in the blood meal, which orchestrates tick development, immunity, and vector competence.

Mercury-Modulated Immune Responses in Arctic Barnacle Goslings (Branta leucopsis) upon a Viral-Like Immune Challenge.

Historical mining activities in Svalbard (79°N/12°E) have caused local mercury (Hg) contamination. To address the potential immunomodulatory effects of environmental Hg on Arctic organisms, we collected newborn barnacle goslings (Branta leucopsis) and herded them in either a control or mining site, differing in Hg levels. An additional group at the mining site was exposed to extra inorganic Hg(II) via supplementary feed. Hepatic total Hg concentrations differed significantly between the control (0.011 ± 0.002 mg/kg dw), mine (0.043 ± 0.011 mg/kg dw), and supplementary feed (0.713 ± 0.137 mg/kg dw) gosling groups (average ± standard deviation). Upon immune challenge with double-stranded RNA (dsRNA) injection, endpoints for immune responses and oxidative stress were measured after 24 h. Our results indicated that Hg exposure modulated the immune responses in Arctic barnacle goslings upon a viral-like immune challenge. Increased exposure to both environmental as well as supplemental Hg reduced the level of natural antibodies, suggesting impaired humoral immunity. Hg exposure upregulated the expression of proinflammatory genes in the spleen, including inducible nitric oxide synthase (iNOS) and interleukin 18 (IL18), suggesting Hg-induced inflammatory effects. Exposure to Hg also oxidized glutathione (GSH) to glutathione disulfide (GSSG); however, goslings were capable of maintaining the redox balance by de novo synthesis of GSH. These adverse effects on the immune responses indicated that even exposure to low, environmentally relevant levels of Hg might affect immune competence at the individual level and might even increase the susceptibility of the population to infections.

Productive and physiological implications of top-dress addition of branched-chain amino acids and arginine on lactating sows and offspring

BackgroundBranched-chain amino acids (BCAAs), including L-leucine (L-Leu), L-isoleucine (L-Ile), L-valine (L-Val), and L-arginine (L-Arg), play a crucial role in mammary gland development, secretion of milk and regulation of the catabolic state and immune response of lactating sows. Furthermore, it has recently been suggested that free amino acids (AAs) can also act as microbial modulators. This study aimed at evaluating whether the supplementation of lactating sows with BCAAs (9, 4.5 and 9 g/d/sow of L-Val, L-Ile and L-Leu, respectively) and/or L-Arg (22.5 g/d/sow), above the estimated nutritional requirement, could influence the physiological and immunological parameters, microbial profile, colostrum and milk composition and performance of sows and their offspring.ResultsAt d 41, piglets born from the sows supplemented with the AAs were heavier (P = 0.03). The BCAAs increased glucose and prolactin (P < 0.05) in the sows’ serum at d 27, tended to increase immunoglobulin A (IgA) and IgM in the colostrum (P = 0.06), increased the IgA (P = 0.004) in the milk at d 20 and tended to increase lymphocyte% in the sows’ blood at d 27 (P = 0.07). Furthermore, the BCAAs tended to reduce the Chao1 and Shannon microbial indices (P < 0.10) in the sows’ faeces. The BCAA group was discriminated by Prevotellaceae_UCG-004, Erysipelatoclostridiaceae UCG-004, the Rikenellaceae_RC9_gut_group and Treponemaberlinense. Arginine reduced piglet mortality pre- (d 7, d 14) and post-weaning (d 41) (P < 0.05). Furthermore, Arg increased the IgM in the sow serum at d 10 (P = 0.05), glucose and prolactin (P < 0.05) in the sow serum at d 27 and the monocyte percentage in the piglet blood at d 27 (P = 0.025) and their jejunal expression of NFKB2 (P = 0.035) while it reduced the expression of GPX-2 (P = 0.024). The faecal microbiota of the sows in Arg group was discriminated by Bacteroidales. The combination of BCAAs and Arg tended to increase spermine at d 27 (P = 0.099), tended to increase the Igs (IgA and IgG, P < 0.10) at d 20 in the milk, favoured the faecal colonisation of Oscillospiraceae UCG-005 and improved piglet growth.ConclusionFeeding Arg and BCAAs above the estimated requirements for milk production may be a strategy to improve sow productive performance in terms of piglet average daily gain (ADG), immune competence and survivability via modulation of the metabolism, colostrum and milk compositions and intestinal microbiota of the sows. The synergistic effect between these AAs, noticeable by the increase of Igs and spermine in the milk and in the improvement of the performance of the piglets, deserves additional investigation.

Abstract P4-07-18: FerOX, an anthracyclines nanoformulation to lead toward immuno-mediated cancer remission, preserving T-cell immune competence

Abstract Background Chemotherapy with anthracyclines, such as doxorubicin (DOX), still remains a mainstay in cancer treatment. DOX kills tumor cells by direct interference with DNA replication, thus it is very effective against highly proliferating cells. Since DOX is not cell-specific drug, it displays severe side effects that limit its clinical use. Besides its direct cytotoxicity, it enhances also tumor immunogenicity, since DOX-induced immunogenic cancer cell death facilitates tumor antigens presentation. However, the generation of an adaptive immune response is one of the most highly- proliferative processes, thus it may be affected by DOX cytotoxicity, paradoxically preventing the establishment of a proper adaptive antitumor immune response. Therefore, the effect of DOX on dividing T-cells urges investigation. Methods We explored the phenotypic and functional effects of DOX on lymphocytes from healthy donors and from breast cancer (BC) patients. Purified peripheral blood mononuclear cells (PBMC) were subjected to an uptake assay and to a CFSE-based proliferation assay in vitro. Characterization of lymphocytes was made by flow cytometry (FC) and confocal microscopy. Innovative DOX nanoformulation with proved efficacy in cancer cell line, BC Patient-derived Organoids (PDO) and murine model of BC, has been assessed in parallel to liposomal DOX, evaluating both DOX uptake and their capability to preserve proliferation potential in different PBMC subpopulation. Results PBMC incubated in vitro with DOX displayed a dose-dependent DOX uptake that results in a dramatic proliferative impairment. The same behavior has been observed in BC patient-derived PBMC, isolated immediately after the end of first cycle of chemotherapy, which show a prompt DOX internalization coupled with a dramatic impairment of proliferative potential in comparison to the match-paired PMBC isolated before the treatment. Interestingly, FC characterization showed that DOX internalization is higher in CD8+ than CD4+ T-cells and mainly affects central memory, effector memory and terminal differentiated effector. Since pivotal to every adaptive immune response is the activation and massive proliferation of T cells from their resting state, we have exploited a DOX formulation in ferritin nanocages (FerOX), that displays a TfR1-mediated tumor specific homing in order to circumvent drug internalization in those immune cells. FerOX efficacy has been proved in BC-PDO, evidencing an inverse correlation between TfR1 expression and HFn-DOX IC50. HFn nanoformulation protects immune cells from DOX toxic effects, reducing DOX uptake and proliferative impairment, mainly preserving Naïve T-cells. The capability of FerOX to preserve T-cells competence to generate an immune response has been corroborated by an in vitro experiment aimed to mimic what could happens to patient’s PBMCs if they could be treated with FerOX. Conclusions As a whole, our data indicate that preventing T- cells chemotherapy-related toxicity through FerOX could allow the host adaptive immune system to fully benefit from the DOX-induced immunogenic cell death to vaccinate against cancer. This strategy could be promising for complete tumor eradication and might generate a long- term immunosurveillance of recurrences and metastases. Citation Format: Serena Mazzucchelli, Francesco Mainini, Francesco Andreata, Marta Truffi, Arianna Bonizzi, Francesca Piccotti, Marta Sevieri, Fabio Corsi. FerOX, an anthracyclines nanoformulation to lead toward immuno-mediated cancer remission, preserving T-cell immune competence [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-18.

O-164 Live yeast supplementation during last month of gestation improves ewes ruminal microbiota, oxidative status, colostrum quality and offspring immune competence

O-164 Live yeast supplementation during last month of gestation improves ewes ruminal microbiota, oxidative status, colostrum quality and offspring immune competence

Potential biomarkers for the prognosis and treatment of HCC immunotherapy.

The liver is a unique organ containing large populations of immune cells. Immunotherapy for liver cancer is a promising yet particularly challenging method. Therefore, it harbors great significance for the identification of immune-related subtypes and the potential therapeutic targets for hepatocellular carcinoma (HCC). Firstly, we classified the HCC samples downloaded from the dataset of Cancer Genome Atlas (TCGA) into two clusters based on the immune cell infiltration. Thereafter, we identified the significant module and regulatory factors using the weighted gene co-expression network analysis (WGCNA). The immune competence of the regulatory factors was delineated through the ESTIMATE algorithm, the analysis of the tumor microenvironment, and pan-cancer analysis. In the single-cell RNA sequencing analysis, we further explored the immune competence of regulatory factors. We also collected the potential drugs targeting the regulatory factors. In addition, we constructed lncRNA-miRNA-mRNA interaction regulatory networks. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to verify the protein expression of regulatory genes in HCC cell lines and tissues. According to the immune cell infiltration, two immune-related subtypes-cluster 1 and cluster 2-were found. Patients in cluster 2 had a more significant immune infiltration than in cluster 1. Afterward, six significant regulatory genes were identified through WGCNA, and the expression in cluster 2 was high in cluster 1. We performed a comprehensive analysis to clarify the immune signature. The results showed that the six genes had significant immunological competence. Moreover, the expression of the six genes was similar to the subtypes' classification. In the analysis of the prognosis value, patients in cluster 2 had a better prognosis. In addition, the lncRNA in the lncRNA-miRNA-mRNA interaction regulatory networks was located in the nucleus and cytoplasm. In the single-cell RNA sequencing analysis, the six genes were related to the immune cell. We also identified potential drugs for CD6 and CLEC12A, which may provide potential therapeutic drugs. Finally, the regulatory genes were verified in the western blot and quantitative real-time polymerase chain reaction. The classification into two clusters based on the immune cell infiltration may provide a promising prospect for HCC through immunotherapy. The six regulatory genes may be potential therapeutic targets in the treatment of HCC.

Preweaning Nutrition and Its Effects on the Growth, Immune Competence and Metabolic Characteristics of the Dairy Calf

Feeding increased volumes of milk in the preweaning phase has been shown to improve growth, morbidity and mortality rates in calves (Bos Taurus). This experiment enlisted 20 Holstein-Friesian dairy replacement calves from birth until weaning (at 10 weeks of age) and assessed the effect of feeding either 4 L (Low) or 8 L (High) of milk per calf per day on their growth, immune competence and metabolic characteristics. The responsiveness of these systems was compared through a vaccination immune challenge. Calves in the High treatment group were significantly heavier from two weeks of age and were 19 kg heavier than calves in the Low treatment group at weaning. Calves in the High treatment group also exhibited greater immune responses, with significantly higher white cell counts and neutrophil counts than calves in the Low treatment group post-vaccination. Calves in the High treatment group also had lower beta-hydroxybutyrate both pre- and post-vaccination, and higher glucose and insulin levels post-vaccination, indicating superior metabolic characteristics. Calves had ad libitum access to lucerne hay (Medicago sativa) and a commercial concentrate. Solid feed intakes were mostly the same between treatments, with differences in hay intake only detected at 7 and 8 weeks of age. Results from this experiment are indicative of a positive influence of accelerated preweaning nutrition on growth, immune response and metabolic characteristics.

Effects of different nutrient supply on metabolism and mammary immune response to an LPS challenge in early lactation of dairy cows

Energy and nutrient deficiency in dairy cows in early lactation is considered to contribute to their increased susceptibility to mastitis. We have tested the hypothesis that feeding diets with high contents of either nitrogenic, glucogenic, or lipogenic components in early lactation affects both the endocrine and metabolic status, as well as the mammary immune competence. After calving, cows were fed increasing amounts of concentrate up to 10 kg/d rich in crude protein (nitrogenic, n = 10), glucogenic precursors (glucogenic, n = 11), or lipids (lipogenic, n = 11). In wk 3, one udder quarter was challenged with lipopolysaccharide (LPS) from Escherichia coli. Blood and milk were sampled on the day before LPS challenge (d -1), and on d 0, 1, 2, 3, and 9 after LPS challenge. On the day of LPS challenge additional samples were taken hourly for quarter milk and every 3 h for blood. Urea concentrations were higher in plasma and milk of cows fed the nitrogenic diet. However, plasma concentrations of glucose, cholesterol, triglycerides, β-hydroxybutyrate, nonesterified fatty acids, as well as insulin, glucagon, and insulin-like growth factor-1 were not affected by the different diets. The mammary immune challenge induced a substantial increase of somatic cell count (SCC) in the treated quarter, and a transient decrease of total milk yield and white blood cells similar in all diet groups for one day. The absolute phagocytosis of blood leukocytes was decreased; however, the phagocytosis per cell was increased in glucogenic-fed cows at 6 h after LPS challenge. During mammary inflammation an insulin resistance, shown by increased plasma glucose, insulin, and glucagon, developed similarly in all diet groups. β-hydroxybutyrate and nonesterified fatty acids were decreased at 1 d after LPS challenge in glucogenic-fed cows only. Cholesterol did not change, and triglycerides only decreased significantly in lipogenic-fed cows 6 h after challenge. On d 9 after LPS challenge, SCC and milk yield and metabolic factors were recovered in all groups. In conclusion, the endocrine and metabolic situation, and the immune response to intramammary LPS of dairy cows during early lactation was not substantially influenced by the elevated supply of nitrogenic, glucogenic, or lipogenic components due to the provided feed in this study.

Nutritional status and effect of highly active anti-retroviral therapy (HAART) on selected trace elements in people living with HIV in Ghana

Background and objectivesEssential trace elements obtained from our diet are crucial for the initiation and development of host defence by the immune system. Trace elements such as selenium (Se), zinc (Zn) and copper (Cu) are important for immune competence, particularly in vulnerable population. Poor nutrition status including deficiencies of these vital elements is associated with immune abnormalities and increased susceptibility to infectious diseases. MethodsA comparative study involving a cohort of three hundred and twenty-five (325) participants comprising: 166 persons living with HIV (PLWH) (consisting of 100 on HAART and 66 HAART-treatment naive) and one hundred and fifty-nine (159) non-HIV controls were recruited. Waist to hip ratio and dietary habits were assessed to determine respondents’ nutritional status. Serum Zn, Se and Cu concentrations were estimated by neutron activation method. ResultsMean body mass index (BMI) of respondents was 24.7±4.8 kg/m2. Dietary recommended intakes (DRIs) of macronutrient [energy (69%), carbohydrates (86%) and fats (76%)] and micronutrient [(vitamin B2 (63%), vitamin D (15%), folate (47%) and calcium (63%)] were not adequately met by all groups. PLWH on HAART had a significantly higher total body fat (p=0.004) and visceral fat (p<0.001). Dietary intake of Se, Zn and Cu were highest among the controls (47.0±5.4 µg, 12.4±2.9 mg and 843±15.2 mg respectively) and least, among the HAART treatment naïve group (10.1±5.6 µg, 2.1±0.9mg and 438±16.3 mg respectively), although serum concentrations were significantly lower (0.63±0.21 µmol/L, 1.33±0.92 µmol/L and 1.12±0.14 µmol/L; p<0.001, respectively). Dietary intake of Se and Cu were not associated with their serum concentrations, but treatment status was significantly associated with their serum concentrations (p-value<0.001). Respondents on Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP) had higher serum Se and Cu concentrations but lower Zn concentrations compared to those on other medications. ConclusionMultiple nutrient intakes among PLWH were not adequate; thus, dietary counseling and micronutrient supplementation are strongly recommended, as food security strategies by stakeholders involved in the nutrition management of PLWH in Ghana are also needed. Intake of AZT + 3TC + NVP may improve serum concentrations of Se, and Cu, but could negatively affect serum Zn concentration.

Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials

Omidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has demonstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide. With a median follow-up of 22 months (range, .3 to 122 months), the 3-year estimated overall survival and disease-free survival were 62.5% and 54.0%, respectively. With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3+, CD4+, CD8+, CD19+, CD116+CD56+, and CD123+ immune subsets revealed median counts remaining within normal ranges through up to 8 years of follow-up. Secondary graft failure occurred in 5 patients (5%) in the first year, with no late cases reported. One case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation. This was also observed in a control arm patient who received only unmanipulated UCB. Overall, omidubicel demonstrated stable trilineage hematopoiesis, immune competence, and graft durability in extended follow-up.

Field recommended concentrations of pyraclostrobin exposure disturb the development and immune response of worker bees (Apis mellifera L.) larvae and pupae.

The strobilurin fungicide pyraclostrobin is widely used to prevent and control the fungal diseases of various nectar and pollen plants. Honeybees also directly or indirectly contact this fungicide with a long-term exposure period. However, the effects of pyraclostrobin on the development and physiology of Apis mellifera larvae and pupae during continuous exposure have been rarely known. To investigate the effects of field-realistic concentrations of pyraclostrobin on honeybee survival and development, the 2-day-old larvae were continuously fed with different pyraclostrobin solutions (100mg/L and 83.3mg/L), and the expression of development-, nutrient-, and immune-related genes in larvae and pupae were examined. The results showed that two field-realistic concentrations of pyraclostrobin (100 and 83.3mg/L) significantly decreased the survival and capped rate of larvae, the weight of pupae and newly emerged adults, and such decrease was a positive correlation to the treatment concentrations. qPCR results showed that pyraclostrobin could induce the expression of Usp, ILP2, Vg, Defensin1, and Hymenoptaecin, decrease the expression of Hex100, Apidaecin, and Abaecin in larvae, could increase the expression of Ecr, Usp, Hex70b, Vg, Apidaecin, and Hymenoptaecin, and decreased the expression of ILP1, Hex100 and Defensin1in pupae. These results reflect pyraclostrobin could decrease nutrient metabolism, immune competence and seriously affect the development of honeybees. It should be used cautiously in agricultural practices, especially in the process of bee pollination.

Immunodeficiency is prevalent in congenital heart disease and associated with increased risk of emergency admissions and death.

To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.

Insights on Mpox virus infection immunopathogenesis.

An immunocompromised status has been associated with more odds of being infected with Mpox virus (MPXV) and progressing to severe disease. This aligns with the importance of immune competence for MPXV control and clearance. We and others have previously reviewed parallels between MPXV and other viruses belonging to the Poxviridae in affecting the immune system. This article reviews studies providing direct evidence of the MPXV-immune interactions. The wide-ranging effects of MPXV on the immune system, from stimulation to modulation to memory, are broadly categorised, followed by a detailing of these effects on the immune cells and molecules, including natural killer cells, macrophages, neutrophils, lymphocytes, cytokines, interferons, chemokines, and complement.

Evaluating tumor cell- and T cell-derived extracellular vesicles as potential biomarkers of cancer and immune cell competence

ABSTRACT Introduction Extracellular vesicles (EVs) produced by tumors, also called tumor-derived exosomes (TEX), have been implicated in inducing immune cell suppression in vitro and in vivo. The development of a novel category of noninvasive biomarkers for precision oncology remains an unmet need, and TEX emerge as a promising liquid tumor biopsy component. Areas covered TEX play a critical role in monitoring cancer presence/progression and in reprograming of anti-tumor effector T cells to producers of EVs with pro-tumor activity. TEX are a subset of circulating EVs. Their separation by immune capture from EVs derived from nonmalignant cells allows for TEX phenotypic/functional assessments. TEX cross-talking with CD3(+) T cells induce the release of CD3(+) small EV (sEV), whose cargo of suppressor proteins resembles that of TEX and further contributes to cancer-induced immune suppression. While TEX recapitulate the genetic/molecular phenotype of tumor cells, CD3(+) sEV might serve as ‘T cell liquid biopsy.’ Expert opinion Preclinical explorations of the role in cancer body fluids of TEX and CD3(+) sEV as cancer biomarkers suggest that these EV subsets may qualify as liquid tumor biopsy noninvasive components in the near future. Their potential to simultaneously serve as noninvasive liquid tumor biopsy and T cell biopsy remains to be validated in future clinical trials.

Torque Teno Virus and Cancers: Current Knowledge

Aim: The aim of this systematic review is to assess the current knowledge about the relationship between Torque Teno virus (TTV) and cancer in different settings. Methods: A systematic search was conducted in Medline via PubMed, Embase and Cochrane Library from the inception to the end of January 2023. Results: 34 articles were included in the qualitative synthesis of this review and 2145 patients with solid tumors have been analyzed. The most prevalent cancer types were hepatocellular carcinoma (HCC) and lung cancer. Conclusion: TTV has proven its role as a marker of functional immune competence in the setting of hematopoietic stem cell transplantation (HSCT), but in the oncological field is yet to be defined.

Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells.

A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.