Local Immune Response Research Articles

Intratumoral microbiota: a new force in the development and treatment of esophageal cancer.

Esophageal cancer (EC) ranks among the most prevalent cancers worldwide, with a particularly high incidence in the Asian population. Due to the inconspicuous nature of early symptoms, patients with esophageal cancer are typically diagnosed in the middle to late stages, resulting in suboptimal overall treatment outcomes. Consequently, there is an urgent need to explore and refine therapeutic strategies. Microorganisms have been identified in numerous tumor tissues, including EC, and these microorganisms are referred to as the intratumoral microbiome. Intratumoral microbiota and their metabolic byproducts can influence the progression and treatment of esophageal cancer through various mechanisms, such as modulating tumor cell metabolism and local immune responses. Therefore, the intratumoral microbiota may potentially serve as a target for the treatment of esophageal cancer. This review delineates the composition, origin, and diagnostic significance of intratumoral microbiota in esophageal cancer tissue, and discusses the mechanisms by which intratumoral microbiota contribute to the onset of esophageal cancer. In addition, the impact of intratumoral microbiota on the treatment of esophageal cancer and its intervention measures are also addressed.

Characterization of HPV6/11-reactive T-cell subsets in papillomas of patients with juvenile-onset recurrent respiratory papillomatosis and identification of HPV11 E7-specific candidate TCR clonotypes.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is caused by persistent infection of epithelial cells by low-risk human papillomavirus (HPV) types 6 and 11. While multiple infiltrated immune cells have been reported to mediate disease progress, knowledge of HPV-reactive T-cell subsets in papillomas remains elusive. Through single-cell RNA sequencing and RNA microarray, we found that CD8+ tissue-resident memory T (CD8+ TRM) cells with strong interferon-gamma (IFN-γ) production expanded, and were negatively correlated to the disease severity in the frequency of surgery. These IFN-γ+ CD8+ memory T cells were readily activated and expanded in vitro by autologous dendritic cells loaded with HPV11 E7 peptide pool. Moreover, T cell receptor (TCR) clonal expansion was observed in JORRP papilloma tissues, indicating a biased TCR repertoire toward HPV-specific recognition. Finally, we identified and characterized HPV11 E7-specific candidate TCR clonotypes from IFN-γ+ CD8+ memory T cells, suggesting their potential application in TCR-engineered T cells (TCR-T) therapy for HPV11-related diseases. Our findings provided insights into the specific local immune response to HPV6/11 infection and highlighted the importance of IFN-γ+ CD8+ TRM cells in anti-HPV6/11 T-cell immunity.IMPORTANCEThe persistent recurrence of human papillomavirus (HPV) 6/11 infection in papillomas underscores the failure of local immune responses in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). Our previous study demonstrated that T cells constitute the predominant immune cell population in JORRP papilloma tissues. Understanding the T-cell-mediated immune responses within JORRP papilloma tissues is crucial for disease control. In the present study, we characterized CD8+ tissue-resident memory T (CD8+ TRM) cells as the primary T-cell subset responsible for local anti-HPV6/11 immunity. Moreover, we identified two HPV11 E7-specific candidate T cell receptor (TCR) clonotypes out of IFN-γ+ CD8+ memory T cells. Overall, our findings provided insights into the local immune responses to HPV6/11 infection and offered information for developing more effective immunotherapeutic strategies against JORRP.

Clinical Insights and Future Prospects: A Comprehensive Narrative Review on Immunomodulation Induced by Electrochemotherapy.

Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects-the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT's potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers.

From fat storage to immune hubs: the emerging role of adipocytes in coordinating the immune response to infection.

Adipose tissue is a rich source of diverse cell populations, including immune cells, adipocytes and stromal cells. Interactions between these different cell types are now appreciated to be critical for maintaining tissue structure and function, by governing processes such as adipogenesis, lipolysis and differentiation of white to beige adipocytes. Interactions between these cells also drive inflammation in obesity, leading to an expansion of adipose tissue immune cells, and the secretion of proinflammatory cytokines from immune cells and from adipocytes themselves. However, in evolutionary terms, obesity is a recent phenomenon, raising the question of why adipocytes evolved to express factors that influence the immune response. Studies of various pathogens indicate that adipocytes are highly responsive to infection, altering their metabolic profiles in a way that can be used to release nutrients and fuel the immune response. In the case of infection with the extracellular parasite Trypanosoma brucei, attenuating the ability of adipocytes to sense the cytokine IL-17 results in a loss of control of the local immune response and an increased pathogen load. Intriguingly, comparisons of the adipocyte response to infection suggest that the immune responses of these cells occur in a pathogen-dependent manner, further confirming their complexity. Here, with a focus on murine adipose tissue, we discuss the emerging concept that, in addition to their canonical function, adipocytes are immune signalling hubs that integrate and disseminate signals from the immune system to generate a local environment conducive to pathogen clearance.

The influence of professional oral hygiene on the indicators of local immunity

Professional oral hygiene is an important part of measures aimed at preventing and maintaining the patient’s health. Local immune response is the first barrier of immune protection capable of preventing infection diseases. The aim of the study - the influence of professional hygiene on the indicators of local immunity has been studied. The study involved two groups of patients: the first group included 19 individuals with chronic caries of varying depths (class I), and the second group comprised 15 individuals with moderate periodontal disease. To evaluate nonspecific oral protection, the index of natural colonization of the buccal epithelium and the activity of microbial adsorption by oral mucosal cells were assessed. Specific immunity was evaluated by measuring the concentration of immunoglobulins in unstimulated saliva. All indicators were recorded both before and after professional oral hygiene procedures. When studying the index of natural colonization of the buccal epithelium, it was found that professional cleaning in both groups led to normalization of the spectrum of bacteria adhered to the epithelium: there was a decrease in the amount of gram-negative microflora, atypical for this biotope, while maintaining a high adhesion index of gram-positive cocci. In persons with caries, before sanation, “unsatisfactory” resistance of oral mucosa was revealed in a third of the examined, after sanation, the number of such patients decreased by 3 times, with “satisfactory” resistance increased by 2 times. In the group with periodontal disease, all patients exhibited “unsatisfactory” mucosal resistance before the hygiene procedures. After sanitation, 20 % “unsatisfactory” resistance persisted. In the majority of patients (80 %), the resistance of the oral mucosa improved to “satisfactory”. The concentration of all classes of immunoglobulins in both groups before sanitation was significantly below the norm, after the measures taken, the indicators increased significantly and reached the level typical for healthy individuals. Carrying out professional cleaning of the teeth leads to the normalization of local immune status even without additional medical immunocorrection.

In Situ Expression of TNF-α and IL-10 in Human Dermatophytosis Lesions due to Trichophyton rubrum.

Dermatophytosis is a very common superficial mycosis, but there are few studies about the human immune response to dermatophytes. We aim to analyze the in situ expression of TNF-α and IL-10 in human dermatophytosis. Expression of TNF-α and IL-10 were evaluated in skin samples from 10 patients with dermatophytosis and 12 healthy subjects using an immunohistochemistry assay. TNF-α and IL-10 were significantly elevated in lesions from patients with dermatophytosis compared to healthy controls. These data illustrate the balance of pro- and anti-inflammatory cytokines suggesting Trichophyton rubrum infection could control the local immune response.

Peculiarities of the regional hemodynamics in patients with mono- and bilateral herpes simplex virus stromal keratitis

Background. Herpes simplex virus keratitis (HSVK) is the main cause of blindness in the world resulted from corneal pathology. The blood circulation system of the eye plays an important role in the effective implementation of the immune response. The purpose of the study: to determine the influence of the factor of laterality of the stromal HSVK on the ocular hemodynamics and the frequency of complications. Material and methods. Primary stromal HSVK (was registered for the first time and lasted no more than 3 months) was diagnosed in 32 people (35 eyes), 205 patients (226 eyes) had recurrent stromal HSVK. Among these patients, stromal HSVK was detected both in one eye — unilateral, and in two eyes — bilateral. Complications of stromal HSVK includes: the presence of a transparent graft — in 23 eyes and its opacity — in 10 eyes, secondary glaucoma — in 6 eyes, condition after corneal ulcer — in 16 eyes. The average age of the patients (M ± SD) is 42.2 ± 15.0 years. The control group consisted of 16 healthy volunteers (32 eyes) of similar age. The standard technique of rheoophthalmogram on the ReoCom computer rheograph (Kharkiv, Ukraine) was used. The following indicators were analyzed: rheographic quotient (RQ, ‰) (pulse volumetric blood filling); α1/T (%) — the tone of the large vessels of the eye; velocity of blood filling V (Ohm/s). Results. Patients with stromal HSVK had mainly monolateral eye lesion — 89.8 %, and bilateral lesion was present in 10.2 % of cases. There were no significant differences in the frequency of laterality between primary and recurrent stromal HSVK. In case of recurrence of complicated unilateral and bilateral stromal HSVK, the volumetric pulse blood filling was 17.6 and 30.3 % lower, respectively, than in uncomplicated course, which determines the insufficiency of blood supply to the eye. The rate of blood filling in complicated stromal HSVK was lower than in uncomplicated one by 23 %. At the recurrence of bilateral stromal HSVK, the RQ was higher by 26.4 %, and the rate of blood filling was higher by 36.3 % compared to unilateral one. There were no differences in remission. The tone of the large vessels of the eye with bilateral stromal HSVK is 14 % lower than with unilateral course. Conclusions. In case of recurrent stromal HSVK, the volume pulse blood filling of the eye and its velocity are higher, and the vascular tone is lower than in case of unilateral one, both uncomplicated and complicated. It is assumed that such a significant activation of the ocular hemodynamics is compensatory and contributes to a greater local immune response and improvement of trophism.

Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Association of PD-L1 immunoexpression with tumor grade in colorectal adenocarcinoma

Globally, colorectal cancer (CRC) is the primary cause of cancer-related deaths, and in emerging countries, its prevalence is continuously increasing. With all the advancements in surgery and treatment, the outlook for CRC patients is still not good. Even with the use of standard prognostic markers, there are presently no effective prognostic techniques for colorectal cancer. The long-term survival of many malignancies has been significantly enhanced by immune checkpoint blockades (ICB), suggesting that the immune checkpoint mechanism is crucial in inhibiting tumor-specific immune responses in the tumor microenvironment. By inhibiting T effector cell activity, the "PD-1 (programmed cell death-1)"/PD-L1 (programmed cell death-ligand 1) axis contributes significantly to immune suppression control and allows tumor cells to evade the host's anti-tumor immune surveillance. While early study suggested that immunotherapy was not relevant for patients with colorectal cancer, more recent studies have demonstrated that immunotherapy was beneficial for a certain subset of patients. This suggests that the prognosis prediction of colorectal cancer may benefit from a thorough evaluation of the local immune response. This study set out to assess the association between PD-L1 immunoexpression and tumor grade in CRC. : This was a cross-sectional observational study. Paraffin blocks of total 64 cases were selected from the patients who were diagnosed as adenocarcinoma from resected samples received in the department of pathology at BSMMU from July 2021 to June 2023. Immuno-histochemical staining for PD-L1 was performed using 28-8 clone along with appropriate positive control. In this study, PD-L1 immuno-expression was found in 14(21.9%) out of 64 cases. However, no expression was found in rest of the 50 (78.1%) cases. This study showed association of PD-L1 expression with high grade (Grade-3) tumors. : Evaluation of expression of PD-L1 may emerge as a new marker and target for the immunotherapy of colorectal cancer.

Dietary Chlorella vulgaris supplementation modulates health, microbiota and the response to oxidative stress of Atlantic salmon

Microalgae are emerging as functional feed ingredients in aquaculture due to their immune-stimulating and stress-modulating properties. We investigated the potential of the microalgae Chlorella vulgaris as a feed supplement to improve the health and modulate microbiota and stress responses of Atlantic salmon. Triplicate groups of Atlantic salmon (~ 126 g) were reared in a recirculating aquaculture system (RAS) at 15 °C and received diets supplemented with 2% (CV2) or 14% (CV14) spray-dried C. vulgaris daily, 14% once weekly (CV14w), or a control diet (CD) for 8 weeks. Subsequently, all groups were exposed to an acute one-hour peracetic acid (CH3CO3H; PAA) treatment, a commonly used disinfectant in RAS. While CV14 increased feed conversion (FCR) significantly, feeding the diets CV2 and CV14w improved protein retention efficiency. CV14 significantly modulated beta-diversity in the intestinal digesta and mucosa, but this effect was already visible in fish fed CV2. Feeding CV14 and, to a lesser degree, CV2 increased the relative abundances of Paenarthrobacter and Trichococcus in the digesta and mucosa, which are able to metabolize complex carbohydrates. However, the same diets reduced the abundance of the lactic acid bacteria Lactobacillus and Weissella in the digesta and Floricoccus in the mucosa. Peracetic acid exposure induced systemic stress (increase in plasma glucose and cortisol) and a local immune response in the gill, with the most prominent upregulation of several immune- and stress-regulated genes (clra, cebpb, marco, tnfrsf14, ikba, c1ql2, drtp1) 18 h after exposure in fish fed the control diet. Fish receiving CV14 once a week showed a reduced transcriptional response to PAA exposure. Catalase protein abundance in the liver increased following exposure to PAA, while superoxide dismutase abundance in the gill and liver was increased in response to C. vulgaris inclusion before stress. Overall, the results highlight that a high (14%) inclusion rate of C. vulgaris in feed for Atlantic salmon impairs feed conversion and shifts the intestinal microbiota composition in digesta and mucosa. Weekly feeding of C. vulgaris proves a viable approach in improving protein retention and improving transcriptional resilience towards oxidative stress in increasingly intensive production systems. Thereby this study may motivate future studies on optimizing temporal feeding schedules for health-promoting aquafeeds.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated positive correlation with interferon-related protein expression and negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insight into the lower airway and systemic proteome of severe pediatric vLRTI.

The developing immune system in preterm born infants: From contributor to potential solution for respiratory tract infections and wheezing.

Moderate-late preterm-born infants experience more frequent and severe respiratory tract infections and wheezing compared to term-born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. Until now, moderate-late preterm infants are underrepresented in research and mechanisms underlying their morbidity are largely unknown, although they represent 80% of all preterm-born infants. In order to protect these infants effectively, it is essential to understand the role of the immune system in early life respiratory health and to identify strategies to optimize immune development and respiratory health. This review elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm-born infants, exploring their impact on the immune system and microbiome. Factors discussed are early life antibiotic use, birth mode, feeding type and living environment. Further, differences in adaptive and innate immune maturation between term and preterm infants are discussed, as well as differences in local immune reactions in the lungs. Finally, preventative strategies are being explored, including microbiota transplantation, immune modulation (through pre-, pro-, syn- and postbiotics, bacterial lysates, vaccinations, and monoclonal antibodies) and antibiotic prophylaxis.

B Cell and Antibody Responses in Bovine Tuberculosis.

The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, Mycobacterium bovis. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B cells and antibodies in bovine tuberculosis has been relatively undervalued and understudied. Current evidence indicates that circulating M. bovis-specific antibodies are not effective in controlling the disease. However, local humoral immune responses may contribute to either defence or pathology. Recent studies in animal models and cattle vaccine trials suggest a potential beneficial role of B cells in tuberculosis control. This review discusses the role of B cells and antibodies in bovine tuberculosis and explores antibody-based diagnostics for the disease, including traditional techniques, such as different ELISA, new platforms based on multiple antigens and point-of-care technologies. The high specificity and sensitivity values achieved by numerous antibody-based tests support their use as complementary tests for the diagnosis of bovine tuberculosis, especially for identifying infected animals that may be missed by the official tests.

Breaking a dogma: orthodontic tooth movement alters systemic immunity

BackgroundThe prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach.Materials and methodsA previously described mouse orthodontic model was used. Ni-Ti. springs were set to move the upper 1st-molar in C57BL/6 mice and the amount of OTM was. measured by µCT. Mice were allocated randomly into four experimental groups, each. corresponding to clinical phases of OTM, relative to force application. Terminal blood. samples were collected and a comprehensive blood count test for 7 cell types as well as. proteome profiling of 111 pivotal cytokines and chemokines were conducted. Two controls. groups were included: one comprised non-treated mice and the other mice with inactivated springs.ResultsSerum immuno-profiling unveiled alterations in cellular immunity, manifesting as. changes in percentages of leukocytes, monocytes, macrophages, neutrophils, and. lymphocytes, alongside key signaling factors in comparison to both control groups. The systemic cellular and molecular alterations triggered by OTM mirrored the dynamics previously described in the local immune response.ConclusionsAlthough the exact interplay between local and systemic immune responses to orthodontic forces require further elucidation, our findings demonstrate a tangible link between the two. Future investigations should aim to correlate these results with human subjects, and strive to delve deeper into the specific mechanisms by which mechanical force modulates the systemic immune response.

A Novel Chimeric Oncolytic Virus Mediates a Multifaceted Cellular Immune Response in a Syngeneic B16 Melanoma Model

Background/Objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored. Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8+ T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings. Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8+ T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.

Distribution of Immunomodulation, Protection and Regeneration Factors in Cleft-Affected Bone and Cartilage.

Craniofacial clefts can form a significant defect within bone and cartilage, which can negatively affect tissue homeostasis and the remodeling process. Multiple proteins can affect supportive tissue growth, while also regulating local immune response and tissue protection. Some of these factors, like galectin-10 (Gal-10), nuclear factor kappa-light-chain-enhancer of activated B cells protein 65 (NF-κB p65), heat shock protein 60 (HSP60) and 70 (HSP70) and cathelicidin (LL-37), have not been well studied in cleft-affected supportive tissue, while more known tissue regeneration regulators like type I collagen (Col-I) and bone morphogenetic proteins 2 and 4 (BMP-2/4) have not been assessed jointly with immunomodulation and protective proteins. Information about the presence and interaction of these proteins in cleft-affected supportive tissue could be helpful in developing biomaterials and improving cleft treatment. Two control groups and two cleft patient groups for bone tissue and cartilage, respectively, were organized with five patients in each group. Immunohistochemistry with the semiquantitative counting method was implemented to determine Gal-10-, NF-κB p65-, HSP60-, HSP70-, LL-37-, Col-I- and BMP-2/4-positive cells within the tissue. Factor-positive cells were identified in each study group. Multiple statistically significant correlations were identified. A significant increase in HSP70-positive chondrocytes in cleft patients could indicate that HSP70 might be reacting to stressors caused by the local tissue defect. A significant increase in Col-I-positive osteocytes in cleft patients might indicate increased bone remodeling and osteocyte activity due to the presence of a cleft. Correlations between factors indicate notable differences in molecular interactions within each group.

Reshaped Local and Systemic Immune Responses Triggered by a Biomimetic Multifunctional Nanoplatform Coordinating Multi-Pathways for Cancer Therapy.

Immunotherapy has fundamentally transformed the clinical cancer treatment landscape; however, achieving intricate and multifaceted modulation of the immune systems remains challenging. Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8). After being camouflaged with a macrophage membrane, the biomimetic nanosystem, named mRDZ, enriched in tumors, which allowed synergistic actions of its components within tumor cells. The chemotherapeutic intervention led to a compensatory upregulation in the expression of IDO1, consequently exerting an inhibitory effect on the reactive oxygen species (ROS) and autophagic responses triggered by DOX and ZIF-8. Precise gene silencing of IDO1 by siIDO1 alleviated its suppressive influence, thereby facilitating increased ROS production and improved autophagy, ultimately bolstering tumor immunogenicity. mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.

Neuro- and immuno-modulation mediated by the cardiac sympathetic nerve: a novel insight into the anti-ischemic efficacy of acupuncture.

Communication between sympathetic nerves and the immune system is a crucial and active process during myocardial ischemia (MI), as myocardial damage and inflammatory stimuli concurrently occur. Sympathetic nerves undergo structural and functional changes after MI, leading to adverse left ventricular (LV) remodeling and heart failure (HF). The complex inflammatory response to MI, including local myocardial anti-inflammatory repair and systemic immune reactions, plays a key role in adverse LV remodeling. Here, we review the progressive structural and electrophysiological remodeling of the LV and the involvement of sympathetic tone in complex and dynamic processes that are susceptible to MI pathological conditions. Acupuncture has been reported to effectively improve cardiac function, eliminate arrhythmia, and mitigate adverse LV remodeling via somatosensory regulation after MI. Moreover, acupuncture has an anti-inflammatory effect on the pathological process of myocardial ischemia. In this Review, we aim to summarize the involvement of sympathetic nerve activation in the neuro-immune modulation of structural and functional cardiac changes after MI. As a noninvasive method for sympathetic regulation, acupuncture is an ideal option because of its anti-ischemic efficacy. A better understanding of the neural circuitry that regulates cardiac function and immune responses following MI could reveal novel targets for acupuncture treatment.

Plasma Interleukin-13 Levels Correlate With the Severity of Symptoms Induced by Functional Dyspepsia.

Functional dyspepsia (FD) is a gastrointestinal functional disorder of the upper gastrointestinal tract that affects the quality of life of patients and poses a significant economic burden. It has been proposed that the local inflammatory immune response at the duodenum is associated with an increase in intestinal permeability, favoring the recruitment of Th2 cells and granulocyte degranulation. Moreover, systemic immune response could also be related to the symptoms of FD. The objective of this study was to evaluate the systemic immune response in Uruguayan patients with FD by analyzing the cytokine levels in plasma and the frequency of circulating T cells associated with duodenal recruitment. An analytic and cross-sectional study in 30 patients with FD and 15 healthy controls (HCs) was carried out. Patients were diagnosed with FD according to the Roma IV Committee definition. Cytokine levels were measured in plasma by a specific assay. Expression of α4β7 and CC chemokine receptor9 in circulating T cells was evaluated by flow cytometry. Higher levels of interleukin (IL)-5, IL-13, and IL-8 and lower levels of IL-10 and IL-12p70 were detected in patients with FD than in HC. Furthermore, a positive linear correlation between IL-13 and the severity of FD symptoms was found. CD4 + T cells from patients with FD expressed higher levels of α4β7 and CC chemokine receptor9 than those from HC. An increase of Th2-like cytokines and a positive correlation between the levels of plasma IL-13 and the severity of symptoms in patients with FD from Uruguay were detected.

SYSTEMIC IMMUNE INFLAMMATION INDEX AND PAN-IMMUNE INFLAMMATION VALUE IN PREDICTING HUMAN LEUKOCYTE ANTIGEN-B27 POSITIVITY: A STUDY ON ANKYLOSING SPONDYLITIS PATIENTS

Objective: Ankylosing spondylitis (AS) is defined as both an auto-immune and autoinflammatory illness. Human leukocyte antigen B27 (HLA-B27), which is extensively employed in the diagnosis of chronic inflammatory diseases, is the basic laboratory parameter of axial spondylarthritis including AS. Systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV), obtained by formulating complete blood count parameters, are promising biomarkers that reflect systemic inflammation and local immune response and predict prognosis in diseases. The aim of this study was to investigate the sensitivity and specificity of SII and PIV biomarkers in predicting HLA-B27 positivity in AS patients. Materials and Methods: The research included 68 individuals with HLA-B27 tests (+) (AS group) and 102 patients with HLA-B27 tests (-) (control group). Results: In the AS group, lymphocyte and mean platelet volume values were determined to be lower than in the control group, while other complete blood count parameters, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were found to be higher. While the SII and PIV values of the AS group determined a positive relation with CRP and ESR levels, they did not show a correlation in the control group. While the sensitivity for PIV in predicting HLA-B27 positivity was found to be 83.80% and the specificity was found to be 84.30%, for SII the sensitivity was found to be 83.80% and the specificity was found to be 86.30%. Conclusion: Easily and rapidly accessible biomarkers SII and PIV can potentially be used to predict HLA-B27 positivity in AS patients.