Immune Changes Research Articles

TMIC-84. MOLECULAR EVOLUTION OF THE TUMOR AND ITS MICROENVIRONMENT AT RECURRENCE

Abstract Changes in the glioma immune microenvironment at recurrence may contribute to disease progression and therapeutic resistance. In prior studies we demonstrated that the circumscribed glioma, pleomorphic xanthoastrocytoma (PXA), was relatively immune enriched including activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages. While PXA are often low-grade, a significant fraction can recur and progress to higher grade. To determine how the tumor and its immune microenvironment changes with recurrence, we examined a cohort of tumors from patients with multiple resections. Using single-nucleus RNA sequencing (snRNAseq) and spatial molecular imaging we investigate the temporal changes in the tumor and its microenvironment. To begin, we analyzed samples from three patients with paired initial and recurrent tumor. A total of 22,465 immune and non-immune cells were analyzed. Compared to the initial, the recurrent tumor tended to have decreased numbers of T cells and T cells had lower expression of CD2 and GZMA. Pathway analysis for DE genes in TAMs demonstrated enrichment of genes associated with NTRK signaling, while pathways related to aerobic respiration and mitochondrial translation were decreased suggesting a less inflammatory phenotype. Tumor cells at recurrence demonstrated decreased expression of CD274 (PD-L1) and of the chemokine CXCL14, previously identified as a factor driving an anti-tumor CD8+ T cell response. In a cohort of 5 patients with paired initial and recurrent tumors, we observed increased numbers of CD163+ TAMs. Together these data suggest changes in the tumor-associated immune response at recurrence that may be relevant to therapy. Using murine models for the disease we are investigating the factors that regulate these changes.

Efficacy and Safety of a Therapy Combining Sintilimab and Chemotherapy With Cryoablation in the First-Line Treatment of Advanced Nonsquamous Non–Small Cell Lung Cancer: Protocol for a Phase II, Pilot, Single-Arm, Single-Center Study

Background Immunotherapy has significantly advanced lung cancer treatment, particularly in nonsquamous non–small cell lung cancer (NSCLC), with overall response rates between 50% and 60%. However, about 30% of patients only achieve a stable disease state. Cryoablation has shown potential to enhance immunotherapy by modifying the tumor’s immune microenvironment through the release of antigens and immune factors. Addressing how to boost the immune response in these patients is critical. Objective This study aims to investigate the efficacy and safety of immunochemotherapy in combination with cryoablation as a first-line treatment for advanced NSCLC. Methods This is a phase II, pilot, open-label, single arm, single center, interventional study. Patients with stage IIIB to IIIC or IV NSCLC with T staging ranging from T1 to T2b will receive sintilimab (200 mg/m2 every 3 weeks) and chemotherapy. After 2 cycles, the feasibility of cryoablation will be considered for those with stable disease by a multidisciplinary team. Cryoablation with 3 freeze-thaw cycles will be performed for the main lesion. The third cycle of systemic therapy will begin 7 (SD 3) days after cryoablation. A total of 20 patients will be enrolled. Treatment will continue until the disease progresses, there is unacceptable toxicity, a participant withdraws consent, other discontinuation criteria are met, or the study reaches completion. The primary objective is to assess progression-free survival (PFS). The secondary objective is to assess efficacy through duration of response, disease control rate, overall survival (OS), and the safety profile. The exploratory objective is to investigate and compare immune factor changes after 2 cycles of immunochemotherapy and at 1, 3, and 7 days after cryoablation. Survival time will be estimated using the Kaplan-Meier method to calculate median PFS and OS. Any adverse events that occur during the trial will be promptly recorded. Results The project was funded in 2024, and enrollment will be completed in 2025. The first results are expected to be submitted for publication in 2027. Conclusions This study will provide evidence for the efficacy and safety of the combination of immunochemotherapy and cryoablation as a first-line treatment for advanced NSCLC. Although it has a limited sample size, the findings of this study will be used in the future to inform the design of a fully powered, 2-arm, larger-scale study. Trial Registration ClinicalTrials.gov NCT06483009; https://clinicaltrials.gov/study/NCT06483009 International Registered Report Identifier (IRRID) PRR1-10.2196/64950

Immune cell changes in Helicobacter pylori infection-induced glandular epithelial cell damage of the gastric mucosa

Objective The purpose of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes. Methods We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori-infected gastric mucosal specimens. Results Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression. Conclusion For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.

Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide

BackgroundKi67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem).MethodRetrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence.ResultsIn control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001).ConclusionGrade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

Multi-omics reveal immune microenvironment alterations in multiple myeloma and its precursor stages

Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. In this study, we aim to systematically characterize the tumor immune microenvironment (TME) and the tumor-immune interactions from precursor stages, i.e., monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), to newly diagnosed MM, comparing these to healthy donors. Using CIBERSORT, mass cytometry (CyTOF), and single-cell RNA sequencing (scRNA-Seq), we examined innate and adaptive immune changes across these stages. We found a decrease in granulocytes in the TME predicts MM outcomes. HLA-DR is reduced in CD16+ monocytes and plasmacytoid dendritic cells, while myeloid dendritic cells show decreased expression of stress and immune-response genes. NK cells and CD8+ T cells shift from a GZMK+ to a GZMB+ cytotoxic phenotype in the TME, with increased inhibitory markers TIM3 and TIGIT. In paired samples, the proportion and gene expression pattern in patient-specific GZMB+CD8+ T cells remain largely unchanged despite MM progression. Our findings provide a comprehensive immune landscape of MM and its precursors, offering insights into therapeutic strategies. Enhancing neutrophil and NK cell cytotoxicity, tumor antigen presentation, and CD8+ T cell versatility in precursor stages may prevent MM progression.

The impact of oral health on depression: A systematic review.

As of 2020, about 21% of adults in the United States have a diagnosable mental health disorder, excluding substance use and developmental disorders. Depression, predicted by the WHO to be the leading cause of disease burden by 2030, is linked to various systemic conditions and has been associated with poor oral health. Both behavioral factors, like poor dental hygiene and irregular visits, and biological mechanisms, such as changes in salivary immunity, contribute to this connection, which impacts overall well-being and quality of life. This systematic review aims include: (1) Does tooth loss affect depression? (2) Does oral pain, such as that experienced during chewing and speaking, impact depression? (3) Does oral functionality, including chewing and speaking, influence depression? (4) Does overall oral health affect depression? We conducted a systematic search of PubMed, EBSCO host, Medline, and Google Scholar databases from January 2000 to June 2024 using relevant keywords. Studies examining the impact of oral health parameters (tooth loss, oral pain, oral functionality, overall oral health) on depression were included. Articles were included if (1) full text manuscripts in English were available, (2) the study described the association of oral health and depression, and (3) the independent value was an oral related factor and the dependent value was depression. The following were excluded from our analysis: (1) any articles where oral factors were not the independent value, (2) systematic reviews, (3) case reports, and (4) duplicate studies among our databases. Thirty-one studies met the inclusion criteria. Tooth loss, oral pain, and impaired oral functionality were consistently associated with increased depressive symptoms across the included studies. Greater tooth loss was linked to higher odds of both onset and progression of depression. Oral pain exacerbated depressive symptoms, while difficulties in chewing or speaking were associated with elevated risks of depression. There is a bidirectional relationship between oral health and depression, highlighting the urgent need for comprehensive public health initiatives. Integrating oral health assessments into routine medical care, and developing targeted interventions are crucial steps to mitigate the impact of poor oral health on mental health outcomes.

Immune defense adaptation of Strauchbufo raddei population in heavy metal polluted area: Insights from developmental and environmental perspectives

The adjustment of immune defense mechanisms is a crucial aspect of biological adaptation to stressful environments. Amphibians, with their unique metamorphic process, experience distinct life stages and exhibit diverse immune defense components. While previous studies have focused on specific immune changes during particular life stages under stress, this research addresses a critical gap by exploring the adaptive immune defense strategies of Strauchbufo raddei in heavy metal-polluted environments. We conducted laboratory experiments, exposing offspring from both polluted and unpolluted areas to control and heavy metal treatments, while continuously monitoring changes in immune components during key metamorphic stages. Notably, we examined the role of the skin microbiome, a crucial but often overlooked barrier against pathogens. The results indicated that individuals from polluted areas exhibited some tolerance to heavy metal exposure, though overall immune function remained diminished. During metamorphosis, when immune defenses are most vulnerable, the skin microbiome rapidly enriched beneficial bacteria, preventing pathogenic colonization and playing a pivotal role in maintaining immune defense in contaminated environments. Moreover, our research highlights energy allocation strategies involving corticosterone and body fat content, enabling populations to maintain development despite immune compromise. The immune adaptations observed may be fixed through genetic assimilation, suggesting a rapid evolutionary response to environmental stress. However, this reduces phenotypic plasticity, making populations more vulnerable to future environmental changes. This study provides key insights into the survival strategies of amphibian populations in heavy metal-contaminated areas, laying the foundation for future research on molecular and evolutionary adaptations.

Obesity uncovers presence of inflammatory lung macrophage subsets with adipose tissue transcriptomic signature in influenza virus infection.

Obesity is a risk factor for increased lung damage and disease severity during influenza virus infection. White adipose tissue (WAT) inflammation is a key driver of disease pathogenesis in obesity. Whether and how obesity modifies lung and WAT immune cell character and function in obesity to amplify influenza disease severity remains unknown. We show that obesity establishes a proinflammatory transcriptome in lung immune cells that is further augmented upon influenza virus infection. Unexpectedly, we also show that influenza virus infection induces expression of inflammatory genes in visceral WAT and modifies WAT immune cell milieu in obesity. Notably, a decrease in WAT macrophage (ATM) populations inversely correlates to increase in infiltrating lung macrophage numbers in obese influenza virus-infected mice. Comparison of both lung and WAT immune cell transcriptional landscapes uncovers a presence of a macrophage subset in the lungs whose transcriptomic signatures matched those of an inflammatory ATM subset preferentially found in obese mice. Adoptive transfer of ATMs from obese mice into lean influenza-virus infected mice promotes host immune cell infiltration to the lungs. Together, our novel findings provide evidence of immune cell transcriptome and character changes in the lungs and WAT of influenza virus infected obese, but not lean, mice and suggest that visceral ATMs may contribute to the overall inflammatory milieu in this setting.

Predictive Value of Immune Activity Changes in Breast Cancer Patients Treated With Dose-dense Neoadjuvant Chemotherapy: A Retrospective Study.

Dose-dense chemotherapy is recommended for patients with breast cancer who have a high recurrence risk. However, whether dose-dense neoadjuvant chemotherapy (ddNAC) improves patient prognoses compared to the normal-dose regimen remains controversial. In this study, we evaluated the predictive value of immune activities on short-term outcomes for patients treated with ddNAC. We classified 82 patients with human epidermal growth factor receptor 2-negative breast cancer treated with NAC into a normal dose group (62 patients) and ddNAC group (20 patients) and examined the differences in clinicopathological features. The ddNAC group was further divided according to patient responses to NAC and the predictive factors for pathological complete response (pCR) were evaluated. There were no differences in the clinicopathological features before NAC between the normal dose and ddNAC groups. Although the pCR rates tended to be higher in the ddNAC group compared than those in the normal dose group (35.0% vs. 25.8%), there was not significant difference (p=0.264). Among all patients treated with ddNAC, the absolute lymphocyte count decreased and the neutrophil-to-lymphocyte ratio increased during dose-dense doxorubicin plus cyclophosphamide treatment. There was no significant correlation between the pCR and any of the clinicopathological parameters tested including systemic peripheral markers and tumor-infiltrating lymphocyte levels. ddNAC affected the levels of systemic peripheral immune markers. However, monitoring these markers may not be useful for predicting responses to ddNAC.

Next Generation of Solid Target Radionuclide Antibody Conjugates for Tumor Immuno-Therapy.

Immune checkpoint therapy has emerged as an effective treatment option for various types of cancers. Key immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and lymphocyte activation gene 3 (LAG-3), have become pivotal targets in cancer immunotherapy. Antibodies designed to inhibit these molecules have demonstrated significant clinical efficacy. Nevertheless, the ability to monitor changes in the immune status of tumors and predict treatment response remains limited. Conventional methods, such as assessing lymphocytes in peripheral blood or conducting tumor biopsies, are inadequate for providing real-time, spatial information about T-cell distributions within heterogeneous tumors. Positron emission tomography (PET) using T-cell specific probes represents a promising and noninvasive approach to monitor both systemic and intratumoral immune changes during treatment. This technique holds substantial clinical significance and potential utility. In this paper, we review the applications of PET probes that target immune cells in molecular imaging.

Mycoplasma pneumoniae: not a typical respiratory pathogen.

Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia among school-aged children and young adults. Infections occur throughout the year but tend to surge during winter months across Europe. A characteristic epidemic cycle, where a substantial surge in the number of infections occurs, is seen approximately every 1-4 years and hypothesized to be driven by changes in immunity and a shift in circulating variants. Once thought to be an organism of low virulence, it has now been found to possess several virulence factors, including toxin production, biofilm formation and evasion of antibody-mediated immunity. The lack of a cell wall and reduced metabolic pathways limit the options for antibiotic treatment. Acquired macrolide resistance is a growing concern, with >80% of cases in China being macrolide-resistant. Although efforts have been made to develop a vaccine, there are still substantial hurdles to overcome in relation to vaccine-enhanced disease, which results from an inappropriate immune response among vaccinated individuals.

Association of Major Histocompatibility Complex Polymorphism With Acute Phase Response in Broiler Chicken.

Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli. This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens. The allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress-related situation. A total of six alleles, ranging from 195 to 448bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p<0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis. Results confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease-resistant traits and resource conservation in commercial broiler chickens.

VSIG4 inhibits the anti-inflammatory reaction of immune cells after cardiogenic shock

Abstract Cardiogenic shock (CS) still has a mortality rate of approximately 50%. CS leads to a significant activation of the immune system. The aim of this study was to characterize the immune cell populations and the immune cell-specific changes in CS on admission to the clinic and after revascularization. We developed a web-based platform named 'IRCaS - Immune Cell Regulations in Cardiogenic Shock' to map the temporal course of immune cell-specific processes of CS after acute myocardial infarction (AMI) from admission to 3 days after revascularization. Our tool revealed an endogenous anti-inflammatory response after CS, which is inhibited by the cell-cell receptor VSIG4. The web platform contains newly acquired single-cell sequencing data from patients with CS after AMI on admission and 24, 48, and 72 hours after revascularisation, as well as controls. In total, 171,962 immune cells derived from peripheral blood mononuclear cells (PBMCs) were individually sequenced. Analysis of the immune cell populations revealed, that 24 hours after revascularisation, monocytes increased to 62.4% (vs. 30.4% in controls), while T cells decreased from 46.3% to 25.0%. On the immune cell expression level, we observed an inflammatory response indicated by IL1B which continuously increased from 24 h (1.6+fold), over 48h (3.1+fold) to 72 h (3.5+fold) after revascularization. Interestingly, there was a significant anti-inflammatory response shortly after revascularization, as evidenced by a transient increase in the anti-inflammatory CD16+ monocyte subpopulation from 12.1% to 26.7% at 24 hours and an increase in THBS1 after revascularization, which was only short-lived. We identified a negative feedback in the increasing anti-inflammatory CD16+ cells caused by a subsequent VSIG4 (+5.2-fold) increase. Indeed, overexpression of VSIG4 in monocytes resulted in a significant decrease of anti-inflammatory CD16+ monocytes by 33.9% and a decrease in anti-inflammatory transcripts. Our data show that in addition to the strong inflammatory response in CS, there is also an opposing anti-inflammatory response, which is however only short-lived, as it is attenuated by a negative feedback via an increase in VSIG4. In addition, our webplatform offers time-dynamic gene expression profiles of immune cells, allowing users to select and visualize specific genes during the course of CS after AMI.

Global deficiency in the inflammatory chemokine receptors 1,2,3 and 5 prevents vascular dysfunction in angiotensin II-induced hypertension and selectively modulates aortic myeloid cell phenotype

Abstract Background Leukocyte migration to the vasculature and the heart plays a critical role in hypertensive immune responses and is a carefully orchestrated process, regulated by the interactions of inflammatory chemokines with their receptors, notably CCR1, CCR2, CCR3, and CCR5 (collectively termed inflammatory chemokine receptors (iCCRs)). However, the inflammatory chemokine/receptor system is characterised by redundancy, ligand sharing and overlapping expression patterns. Consequently, our understanding of the specific and combinatory roles of chemokine receptors in cardiovascular inflammation remains incomplete, thus hindering the development of targeted therapies. To address this challenge, we have utilised two novel mouse models: iREP mice, carrying fluorescent reporters of inflammatory chemokine receptor expression, and TACKO mice, in which the entire iCcr locus containing Ccr1, Ccr2, Ccr3, and Ccr5 has been deleted. Purpose To evaluate the expression pattern of iCCRs in experimental hypertension and understand how the global deletion of iCCRs impacts disease progression. Methods We induced hypertension in mice by subcutaneously implanting osmotic minipumps administering angiotensin II (Ang II) for a duration of 14 days. Single-cell RNA sequencing was utilised for investigating iCCR expression in aortas during hypertension. Additionally, we employed flow cytometry and confocal microscopy to track iCCR expression and localization in aortas and hearts obtained from iREP mice. TACKO mice were utilised to assess the effect of global iCCr deficiency on hypertensive phenotypes. Blood pressure was measured via telemetry and vascular function was assessed using myography. Vascular and heart remodelling were evaluated through histology. Molecular mechanisms were analysed using Western Blotting and RT-qPCR, while immune cell changes in the aorta were evaluated through cytometry of time-of-flight (CyTOF). Results Ang II infusion induced higher iCCRs expression levels in both the aorta and the heart in comparison with sham treatment, particularly in fibrotic areas. After Ang II-treatment, global deletion of iCCRs in TACKO mice resulted in the prevention of endothelial dysfunction (n=5/group, P&amp;lt;0.05) and perivascular fibrosis (n=6-9, P&amp;lt;0.01), and a reduction in cardiomyocyte size (n=12-16, P&amp;lt;0.01) compared to wild type mice. However, no significant improvements were observed in other hypertensive phenotypes, including blood pressure, heart fibrosis, vascular NO synthase, and oxidative stress. CyTOF analysis revealed reductions in inflammatory monocytes and conventional type 2 dendritic cells in TACKO aorta, accompanied by a phenotypic switch in macrophages towards a less inflammatory phenotype. Conclusion Deficiency in iCCRs confers protective effects against vascular dysfunction in experimental hypertension, primarily by selectively reducing inflammatory myeloid cell homing to the aorta.

Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process

The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas unknown_T cells were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift- myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). The shift- myeloid signature was also found to be associated with KD treatment resistance, and effective therapies improve treatment outcomes by reducing this signaling. Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model PHARE (https://xiazlab.org/phare/), which can apply to both scRNA-seq and bulk RNA-seq data. Using this model, we found patients with coronary artery disease (CAD) also exhibit accelerated aging compared to healthy individuals. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

Epicutaneous house dust mite (HDM)-induced skin lesions feature early activation of T helper 2 inflammatory and pruritogenic pathways in HDM-nonsensitised dogs.

Epicutaneously house dust mite-sensitised (HDM-S) healthy dogs are commonly used as canine atopic dermatitis (cAD) models; however, the exact mechanisms of HDM-induced AD immune activation in HDM-S and HDM-nonsensitised (NS) dogs remain unclear. To characterise the inflammatory and pruritogenic transcriptome of acute epicutaneous HDM-induced skin lesions at 6 h and 24 h in HDM-NS and HDM-S dogs; untreated skin at 0 h from each dog served as control. Six HDM-S and six HDM-NS laboratory beagles. Processed expression data from GEO deposited by Schamber etal. (G3 (Bethesda), 2014, 4 and 1787) (GSE58442) were downloaded and analysed using R and the Bioconductor package. Significance analysis was performed with the limma package; genes with false discovery rate <0.05 and fold-change ≤/≥1.5 were considered significantly differentially expressed (DEGs). A 2D principal component analysis revealed no clear separation between HDM-NS and HDM-S dogs at 6 h and 24 h time points. HDM-induced skin lesions in sensitised and nonsensitised dogs at the 24 h time point showed significant upregulation of T helper cell (Th)2 genes (interleukin [IL]-4R, IL-5, IL-13, CCL13 and CCL17), as well as proinflammatory- (LTB, IL-1A and IL-18), Th1- (CXCL10, OASL and MX-1) and Th17-related markers (IL-17B, IL-17F, CCL19 and CCL20). The key Th22-related maker, IL-22, was upregulated only in the HDM-S group at the 24 h time point. Both groups at 24 h featured significant upregulation of several noncytokine pruritogens, such as trypsin, chymase, cathepsin S, periostin and neuromedin B. Taken together, we establish that epicutaneous HDM patch application induces immune changes in HDM-NS dogs with Th2 dominance and activates several itch-promoting pathways.

Cancer new treatment series: Comparison immune changes of HCC by scRNA-Seq following HELC treatment one case study

Immunotherapy has emerged as a novel treatment strategy for many types of cancers, among them, liver cancer. The major advances and achievements in recent years is the use of programmed death-1 (PD-1) blockers for cancer treatment. Since patients’ immune systems are already weak following concurrent surgery plus chemo or radiotherapy, it is necessary to restore and awake their immune cells to maximize the effect for immune therapy. Methods: Liver cancers were treated twice with hapten enhanced local chemotherapy (HELC) like tumor lysates vaccine and following PD-1. Single-cell RNA sequencing (scRNA-seq) was used to analyze the changes of immune responses prior and after treatments. Results: We observed upregulation of cytotoxicity-related genes of CD8 effector T cells and NK cells in untreated tumor; Both Bmem and Naive B cells in untreated tumor showed a significant increase in MHC II signaling pathway-related genes, while MHC I-related genes was upregulated in plasma cells. Significant tumor size shrinkage was observed in both treated and untreated tumors following the HELC+PD-1 therapy. Conclusions: This study provides new biological insights into the abscopal effect at the single-cell level related to the composition of T and B cells in untreated liver cancers before and after major primary tumors treated by HELC. Our data showed that intra-tumor HELC can kill tumor cells and induced immune activity, which is likely vital in modifying tumor associate antigens (TAAs) into neo TAAs. It induces immune response just like vaccine can wake up immune cells and therefore increasing the efficacy of PD1 therapy.

An increase of the oncogenesis frequency is associated with the DAMPs accumulation and the killer cell subpopulations ratio change in patients with long-term post-COVID-19 syndrome

In patients with malignant lesions of the lungs and pancreas, the development of which was facilitated by the long-term post-COVID-19 syndrome (PCS), presence a significant increase (on average by 80%) in the serum content of the cytotoxic oligonucleotide fraction DAMP was found. High antigenic load due to the increase of DAMP contributed to the absorptive function growth and insufficient digestive function of neutrophils; decrease in the NADPH-catalase activity reserve in oxygen-dependent phagocytosis. An increase of CD16+ NK cells of innate immunity and an overexpression of CD8+ killer/suppressor T lymphocyte receptors of adaptive immunity in response to the suppressor coreceptors competitive action were revealed. These changes in cellular immunity were more pronounced in patients with malignant lung lesions and correlated with low serum conductivity. To predict the individual course of the disease, it is advisable to carry out screening measurements of electrical conductivity of blood serum and to determine the control points of innate and adaptive immunity changes in patients with comorbid pathology: PCS and an oncological process. In further studies, attention should be paid to the algorithm development of immunological and screening tests for the oncological diseases course prognosis and the treatment tactics effectiveness.

Dietary Chlorella vulgaris mitigates aflatoxin B1 toxicity in broiler chicken: Toxicopathological, hematobiochemical and immunological perspectives

Mycotoxins are the chemical substances, produced as the secondary metabolites of some toxigenic species of fungi which cause critical health issues in humans, birds and different animal species while Chlorella vulgaris (CV) is a unicellular microalga which contains plenty of important nutritional ingredients. This study was planned to evaluate the toxicopathological, hematobiochemical and immune changes incurred by dietary supplementation of aflatoxin B1 (AFB1) and their mitigation through CV in broilers. For this study to be conducted, 180 broiler birds of one day old were uniformly distributed into six (06) groups and administered various combinations of AFB1 (200 μg/kg) or CV (0.5 and 1.0%) and the duration of the experiment was 42 days. Parameters deliberated were body weight, feed intake, relative visceral organ weights, gross and histopathological examination, hematological parameters (erythrocytic and leukocytic count, hematocrit and hemoglobin), serum biochemical analysis (serum total proteins, ALT, globulin, albumin, creatinine and urea), humoral response against sheep RBCs, response to subcutaneous injection of phytohemagglutinin-P and phagocytic system function assay. The results of this experiment confirmed that 1.0% CV efficiently mitigated AFB1 induced alterations in the studied parameters while this mitigation was partial when 0.5% CV was used with AFB1. Further studies in this regard are still needed to investigate the exact AFB1:CV ratio responsible for complete amelioration.

Analysis of antibody dynamics in Chinese children aged 1-3 years after single-dose varicella vaccination: A 42 months prospective study

ABSTRACT In China, children aged 12 months receive only a single dose of the varicella vaccine and the incidence of varicella remains high. This study aims to evaluate the changes in immunity among children aged 1–3 years following a single dose of the varicella vaccine, providing a scientific basis for determining the optimal age for a second vaccination. This prospective cohort study employed glycoprotein enzyme-linked immunosorbent assay (gpELISA) for antibody detection. The changes in IgG antibody levels over time post-vaccination were analyzed using a restricted cubic spline (RCS) fitted binary logistic regression model. Varicella surveillance data were collected from the National Notifiable Disease Reporting System (NNDRS). Following a peak in varicella incidence in 2019, the incidence shifted toward older age groups. The cohort study results revealed a seropositivity rate of 100% in children during the 18 months post-vaccination, which subsequently declined to 71.6% by the 42 months. The geometric mean concentration (GMC) decreased from 307.6mIU/mL to 115.2mIU/mL. Additionally, 14 children contracted varicella during the follow-up period, resulting in a breakthrough rate of 2.85%. RCS analysis indicated that antibody levels fell below the protective threshold 18.69 months post-vaccination, with a non-linear decline in the odds ratio(OR) of maintaining antibody concentrations ≥ 50mIU/mL(p < .001, Pnonlinear ≤ 0.001). This study demonstrates that the long-term protective efficacy of a single dose of the varicella vaccine diminishes over time in children, underscoring the necessity of implementing a two-dose vaccination strategy. The findings provide scientific evidence for determining the optimal timing for administering the second dose of the vaccine.