Immune System In Patients Research Articles

Approaches to correction of immune system disturbances in post-COVID patients

SARS-CoV-2 virus can induce immune system disorders in post-COVID patients, which may persist for an extended period beyond the acute phase of the disease. Therefore, the search for immunocorrection approaches to address the detected disorders is a significant challenge in clinical immunology. This study aimed to investigate the impact of a synthetic peptide derived from the active center of GM-CSF on the immune system of patients with post-COVID immunopathological syndrome. A total of 21 patients who previously suffered with SARS-CoV-2 infection were included in the study. Flow cytometry was used to analyze various immune cell populations, including panleukocyte markers for gated lymphocytes (CD45+ and CD46+), T lymphocytes (CD3+), helper inducers (CD3+, CD4+), cytotoxic T lymphocytes (CD3+, CD8+), TNK cells (CD3+, CD56+), natural killer cells (CD3-, CD56+), B lymphocytes (CD3-, CD19+), activated helper cells (CD3+, CD4+, CD25+), and activated T lymphocytes (CD3+, HLA-DR). Moreover, IgA, IgM, IgG antibodies specific to SARS-CoV-2, phagocytosis and NBT activity of neutrophils, and complement fragments C1q, C3a, and C5a were assessed. The results demonstrated that topical application of the synthetic peptide derived from the active center of GM-CSF (Acegram-spray) upon mucous membranes significantly influenced the functional bactericidal activity of neutrophils (NBT-activity), increased the percentage of T helper cells, and elevated the C3a complement fragment. These findings indicate that the synthetic peptide primarily affects innate immunity factors. However, no significant differences were observed in other immune system parameters. Therefore, the development of therapeutic approaches for post-COVID patients with impaired immune systems may require a search for additional immunomodulators that target T, B, and NK cells. Further research is needed to explore the effects of various immunomodulators on the immune system of post-COVID patients.

The influence of gut microbiota on immunotherapy for Colorectal Cancer

Colorectal cancer (CRC) is the third most prevalent cancer globally and the second deadliest cancer for both men and women. To change this situation, novel therapeutic approaches have been developed, with immunotherapy being one of the most promising. This technique employs the patient's immune system to identify and eradicate cancer cells. The intestinal microbiota is composed of various microorganisms, such as bacteria, viruses, protozoa, and fungi. This microbiome has vital functions for the human being, such as participation in digestion, vitamin production, protection against aggressive pathogens, and modulation of the immune system. Dysregulation of this homeostasis can generate injuries to the affected person, one of which is carcinogenesis. From this, the intestinal microbiota assumed a relevant role in this therapeutic process by acting in immunotherapy through its participation in blocking some immune checkpoints and, consequently, resulting in a greater efficiency in the cytotoxic activity of T cells. Therefore, this review aims to comprehend the mechanism by which the microbiota directly impacts the development of CRC and, especially, the mechanisms by which the microbiome generates better prognosis in cancer patients.

Effect of COVID-19 on Public Health: The Latest Physical Activity and Diet Update for Counteracting New Emerging COVID-19 Strains (Omicron) and Stay Active and Do Not Lay on the Vaccine Alone: A Narrative Review

Context: Omicron is a new type of SARS-CoV-2 that is considered the most dangerous one so far because despite emerging new variants such as XE, no more dangerous strain than omicron has been identified. On November 24, 2021, World Health Organization identified the Omicron as a global threat. High genetic mutations of Omicron makes it more dangerous than other SARS-CoV-2 variants. This manuscript conducted to systematically collect and provide the effect of COVID-19 on public health: The latest physical activity and diet update for counteracting new emerging COVID-19 strains (Omicron) and stay active and do not lay on the vaccine alone. Evidence Acquisition: We searched PubMed, Web of Science, Embase, and Scopus from January 2020 to November 2021. 3241 articles related to COVID-19 were found and based on filters such as: Physical activity, Omicron, nutrition, immune system, 36 research articles were studied. Results: Studies have shown that regular exercises with low and moderate intensity can have a favorable effect by improving the function of the immune system in reducing the risks of COVID-19 disease. Also, proper nutrition, especially if it is combined with regular exercise, has favorable effects on the immune system of patients with COVID-19. Conclusions: It seems that regular and long-term physical activity with low to moderate intensities (not high intensities) considering a suitable diet regime can have a favorable effect on the immune system of patients with COVID-19.

Hashimoto's disease - the role of factors and diet in the course of the disease

Introduction: Hashimoto's disease is an autoimmune disorder that develops as a result of a pathological reaction of the patient's immune system, which consequently destroys the body's own healthy cells and tissues. Genetic, environmental and immunological factors influence its development. The disease may initially be asymptomatic. The exact aetiology of the disease is unknown. The worldwide incidence is approximately 10-12%.
 Purpose: This paper aims to present the influence of genetic factors, environmental factors, trace elements, and diet on the development and course of Hashimoto's disease based on the current state of knowledge.
 Conclusions: Hashimoto's disease is a multifactorial disease, but the relevance of all factors presented in the development and progression has not yet been confirmed. To date, a special diet for patients has not been created. Further research is needed to better understand the pathogenesis of the disease in order to help patients control HT.
 Methods: Data for the article were retrieved using PubMed setting the time descriptors to 2013-2023.

Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma

The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response.

EXABS-241-LYM Harnessing the Immune System in Patients With Lymphoma

EXABS-241-LYM Harnessing the Immune System in Patients With Lymphoma

Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.

Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.

Cancer Vaccine Therapeutics: Limitations and Effectiveness-A Literature Review.

In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development.

Marine Antimicrobial Peptide Epinecidin-1 Inhibits Proliferation Induced by Lipoteichoic acid and Causes cell Death in non-small cell lung cancer Cells via Mitochondria Damage.

Non-small cell lung cancer (NSCLC) is among the deadliest cancers worldwide. Despite the recent introduction of several new therapeutic approaches for the disease, improvements in overall survival and progression-free survival have been minimal. Conventional treatments for NSCLC include surgery, chemotherapy and radiotherapy. Except for surgery, these treatments can impair a patient's immune system, leaving them susceptible to bacterial infections. As such, Staphylococcus aureus infections are commonly seen in NSCLC patients receiving chemotherapy, and a major constituent of the S. aureus cell surface, lipoteichoic acid (LTA), is thought to stimulate NSCLC cancer cell proliferation. Thus, inhibition of LTA-mediated cell proliferation might be a useful strategy for treating NSCLC. Epinecidin-1 (EPI), a marine antimicrobial peptide, exhibits broad-spectrum antibacterial activity, and it also displays anti-cancer activity in glioblastoma and synovial sarcoma cells. Furthermore, EPI has been shown to inhibit LTA-induced inflammatory responses in murine macrophages. Nevertheless, the anti-cancer and anti-LTA activities of EPI and the underlying mechanisms of these effects have not been fully tested in the context of NSCLC. In the present study, we demonstrate that EPI suppresses LTA-enhanced proliferation of NSCLC cells by neutralizing LTA and blocking its effects on toll-like receptor 2 and interleukin-8. Moreover, we show that EPI induces necrotic cell death via mitochondrial damage, elevated reactive oxygen species levels, and disrupted redox balance. Collectively, our results reveal dual anti-cancer activities of EPI in NSCLC, as the peptide not only directly kills cancer cells but it also blocks LTA-mediated enhancement of cell proliferation.

Harnessing the Immune System: Current and Emerging Immunotherapy Strategies for Pediatric Acute Lymphoblastic Leukemia.

Treatment for relapsed acute lymphoblastic leukemia (ALL) in children and young adults continues to evolve. Despite optimization of cytotoxic chemotherapeutic approaches and risk-adapted therapy, about 12% of pediatric patients still relapse, and survival rates in this population remain poor. Salvage therapy for relapsed patients continues to be challenging as attempts to further intensify chemotherapy have resulted in excessive toxicity without improving outcomes. Immunotherapy has profoundly impacted the landscape of relapsed ALL by harnessing the patient's immune system to target and eliminate leukemia cells. In this review, we provide an overview and summary of immunotherapy agents that have been approved and remain under investigation for children, including blinatumomab, inotuzumab, daratumomab, and chimeric antigen receptor T-cell therapy. We discuss the landmark clinical trials that have revolutionized the field and provide an update on ongoing clinical trials involving these agents for children in the relapsed and upfront setting. The incorporation of these novel immunotherapies into ALL treatment, either as monotherapy or in combination with cytotoxic chemotherapy, has demonstrated promising potential to augment outcomes while decreasing toxicity. However, we also highlight the many challenges we still face and the research critically needed to achieve our goals for cure in children.

Identification of Gene Markers Associated with COVID-19 Severity and Recovery in Different Immune Cell Subtypes.

As COVID-19 develops, dynamic changes occur in the patient's immune system. Changes in molecular levels in different immune cells can reflect the course of COVID-19. This study aims to uncover the molecular characteristics of different immune cell subpopulations at different stages of COVID-19. We designed a machine learning workflow to analyze scRNA-seq data of three immune cell types (B, T, and myeloid cells) in four levels of COVID-19 severity/outcome. The datasets for three cell types included 403,700 B-cell, 634,595 T-cell, and 346,547 myeloid cell samples. Each cell subtype was divided into four groups, control, convalescence, progression mild/moderate, and progression severe/critical, and each immune cell contained 27,943 gene features. A feature analysis procedure was applied to the data of each cell type. Irrelevant features were first excluded according to their relevance to the target variable measured by mutual information. Then, four ranking algorithms (last absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and max-relevance and min-redundancy) were adopted to analyze the remaining features, resulting in four feature lists. These lists were fed into the incremental feature selection, incorporating three classification algorithms (decision tree, k-nearest neighbor, and random forest) to extract key gene features and construct classifiers with superior performance. The results confirmed that genes such as PFN1, RPS26, and FTH1 played important roles in SARS-CoV-2 infection. These findings provide a useful reference for the understanding of the ongoing effect of COVID-19 development on the immune system.

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients.

Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. AML (R20-014), Femicare.

Evidence-based modalities in the management of Psoriasis and Psoriatic arthritis.

Psoriasis is a waxing and waning skin disorder, often associated with a plethora of co-morbidities, including psoriatic arthritis (PsA), a severe form of chronic inflammatory arthritis. All forms of psoriasis and PsA are immune-mediated diseases where the patient's immune system is overactive in the production of certain factors that stimulate and activate the function of certain immune cells. Recent evidence has uncovered an important role for cell-mediated immunity in the aetiology and course of psoriasis and PsA, with a critical role played by the pro-inflammatory IL-23/TH17 axis. Taken together, these new lines of evidence suggest new and improved therapeutic interventions for patients with psoriasis and PsA. The hypothesis-driven process of inquiry of the best available evidence and its implication, application and evaluation in the context of clinical practice pertains to the meta-science of evidence-based health care (EBHC). EBHC consists in the initial step of research synthesis and generation of the systematic review of the best available evidence, estimated both qualitatively and quantitatively (i.e., meta-analysis). Evidence-based decision-making, a process driven and controlled by the expertise of the clinician and by the clinical needs and personal wants of the patient, is the principal, most timely and critical aspect of evidence-based practice. Recent and systematic reviews for the treatment of psoriasis and PsA consistently updated for emerging new and revised data (i.e., living systematic reviews) confirm the efficacy and the effectiveness of methotrexate (MTX) in containing and controlling psoriasis. The outcomes of MTX intervention for PsA remain mixed and inconclusive.

O-143 Biopsy-free profiling of the uterine immune system in patients with recurrent pregnancy loss and unexplained infertility

Abstract Study question What are the differences in menstrual blood lymphocytes between controls, patients with recurrent pregnancy loss (RPL) or with unexplained infertility (uINF)? Summary answer Compared with controls, RPL- and uINF patients had a different menstrual blood immune profile, including altered NK-subtypes indicating an altered cytotoxicity in these patients. What is known already T-cells, particularly regulatory T-cells, and uterine natural killer cells play a vital role as they are the main immunological regulators at the feto-maternal interface. However, an endometrial biopsy (EB) is required for the examination of these cells, necessitating an invasive and uncomfortable procedure. Moreover, the small tissue samples are mainly analyzed by immunohistochemistry, limiting the amount of analysable markers and ultimately results in controversial data. Menstrual blood (MB) has been used in proof-of-concept studies to analyse lymphocyte populations. So far, no study has investigated MB lymphocytes in a well-defined cohort of RPL- and uINF patients in comparison to healthy controls. Study design, size, duration In this prospective study, 46 healthy controls, 28 RPL patients and 11 uINF patients were included between 03/2021 and 02/2022. RPL was defined as ≥ 3 consecutive pregnancy losses. For being diagnosed with uINF, all standard-diagnostic procedures for infertility had to provide negative results in couples trying to conceive for >12 months. Participants/materials, setting, methods To establish the procedure, lymphocyte compositions in EB in 7 controls were compared with those in MB during 48h. The first 24h and the second 24h were collected separately. In all other RPL- and uINF-patients, as well as controls, peripheral blood (PB) and MB was collected. Density gradient centrifugation was performed to isolate PB and MB mononuclear cells. Cells were analyzed by flow cytometry focusing on the main lymphocyte populations and NK-cell subsets. Main results and the role of chance The first 24h of MB closely resembled the uterine lymphocyte composition in EB, with were CD3+ T-cells and CD56+ NK-cells being the predominant lymphocyte populations in EB and MB. We therefore based further analyses on the first 24h of menstrual shedding. In comparison to controls, RPL-patients showed significantly higher MB-CD56+-NK-cell numbers (mean±SD: 31.13±7.52 vs. 36.73±5.4; p = 0.002). Furthermore, MB-CD56dimCD16bright NK-cells within the CD56+-NK-cell population were decreased in individuals with RPL and uINF compared to controls (mean±SD: 20.4±11.53;16.34±14.65;15.7±5.91; Ctrl vs. RPL p = 0.011; Ctrl vs. uINF p = 0.02). Further, compared to controls and RPL patients, uINF patients had lower CD3+ T-cell counts (mean±SD Ctrl. vs. uINF: 47.93±11.11 vs. 38.81±5.04, p = 0.013), with decreased CD4+ (mean±SD Ctrl. vs. uINF: 25.78±7.91 vs. 15.66±4.88, p = 0.001) and CD8+ T-cells (mean±SD Ctrl. vs. uINF: 15.32±4.14 vs. 8.43±2.85, p < 0.001). Interestingly, uINF-patients showed higher CD25highCD127dim/neg regulatory T-cell counts than controls (mean±SD Ctrl. vs. uINF: 1.34±0.49 vs. 1.84±0.51, p = 0.009). The cytotoxicity receptors NKp46 and NKG2D were more present in uINF and RPL patients. Furthermore, RPL and uINF patients had significantly higher peripheral CD56+-NK-cell counts as compared to controls (mean±SD: 8.4±3.5;11.42±4.05;12.86±4.29; Ctrl vs. RPL p = 0.021; Ctrl vs. uINF p = 0.009). Limitations, reasons for caution The small sample size of our study limits our ability to extrapolate the findings to other populations, as well as perform further subgroup analyses in controls, RPL and uINF. Future research must concentrate on NK cell subpopulations in larger cohorts, potentially in a multi-center setting. Wider implications of the findings Strengths of this study include well phenotyped participants and that the immunological milieu of the endometrium is directly compared for EB and MB. In future studies, this non-invasive analysis might enable to identify and monitor patients who could profit from (immunomodulatory) medications, and thereby improve live birth rates. Trial registration number not applicable

Chimeric antigen receptor T-cells: Properties, production, and quality control.

Chimeric antigen receptor (CAR) T-cell therapy is a novel adoptive T-cell immunotherapy for haematological malignancies. First introduced into clinical practice in 2017, CAR T-cell therapy is now finding its place in the management of lymphoid malignancies, primarily of B-cell lineage, including lymphoblastic leukaemia, non-Hodgkin lymphoma and plasma cell myeloma, with remarkable therapeutic outcomes. CAR T-cells are a customised therapeutic product for each patient. Manufacture commences with collection of autologous T-cells, which are then genetically engineered ex vivo to express transmembrane CARs. These chimeric proteins consist of an antibody-like extracellular antigen-binding domain, to recognise specific antigens on the surface of tumour cells (e.g. CD19), linked to the intracellular co-stimulatory signalling domains of a T-cell receptor (e.g. CD137). The latter is required for in vivo CAR T-cell proliferation, survival, and durable efficacy. Following reinfusion, CAR T-cells harness the cytotoxic capacity of a patient's immune system. They overcome major mechanisms of tumour immuno-evasion and have potential to generate robust cytotoxic anti-tumour responses. This review discusses the background to CAR T-cell therapies, including their molecular design, mechanisms of action, methods of production, clinical applications and established and emerging technologies for CAR T-cell evaluation. It highlights the need for standardisation, quality control and monitoring of CAR T-cell therapies, to ensure their safety and efficacy in clinical management.

Impact of radiation on host immune system in patients treated with chemoradiotherapy and durvalumab consolidation for unresectable locally advanced non-small cell lung cancer.

The optimal modalities of radiotherapy when combining concurrent chemoradiation (CCRT) and immunotherapy (IO) for locally advanced non-small cell lung cancer (LA-NSCLC) remain to be determined. The aim of this study was to investigate the impact of radiation on different immune structures and immune cells in patients treated with CCRT followed by durvalumab. Clinicopathologic data, pre- and post-treatment blood counts, and dosimetric data were collected in patients treated with CCRT and durvalumab consolidation for LA-NSCLC. Patients were divided into two groups according to the inclusion (NILN-R+) or not (NILN-R-) of at least one non-involved tumor-draining lymph node (NITDLN) in the clinical target volume (CTV). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Fifty patients were included with a median follow-up of 23.2 months (95% CI 18.3-35.2). Two-year PFS and 2-year OS were 52.2% (95% CI 35.8-66.3) and 66.2% (95% CI 46.5-80.1), respectively. In univariable analysis, NILN-R+ (hazard ratio (HR) 2.60, p = 0.028), estimated dose of radiation to immune cells (EDRIC) >6.3 Gy (HR 3.19, p = 0.049), and lymphopenia ≤ 500/mm3 at IO initiation (HR 2.69, p = 0.021) were correlated with poorer PFS; lymphopenia ≤ 500/mm3 was also associated with poorer OS (HR 3.46, p = 0.024). In multivariable analysis, NILN-R+ was the strongest factor associated with PFS (HR 3.15, p = 0.017). The inclusion of at least one NITDLN station within the CTV was an independent factor for poorer PFS in the context of CCRT and durvalumab for LA-NSCLC. The optimal sparing of immune structures might help in achieving better synergy between radiotherapy and immunotherapy in this indication.

Immunology and immunotherapy in gastric cancer.

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. As the diagnosis of early gastric cancer is difficult, most patients are at a late stage of cancer progression when diagnosed. The current therapeutic approaches based on surgical or endoscopic resection and chemotherapy indeed improve patients' outcomes. Immunotherapy based on immune checkpoint inhibitors has opened a new era for cancer treatment, and the immune system of the host is reshaped to combat tumor cells and the strategy differs according to the patient's immune system. Thus, an in-depth understanding of the roles of various immune cells in the progression of gastric cancer is beneficial to application for immunotherapy and the discovery of new therapeutic targets. This review describes the functions of different immune cells in gastric cancer development, mainly focusing on T cells, B cells, macrophages, natural killer cells, dendritic cells, neutrophils as well as chemokines or cytokines secreted by tumor cells. And this review also discusses the latest advances in immune-related therapeutic approaches such as immune checkpoint inhibitors, CAR-T or vaccine, to reveal potential and promising strategies for gastric cancer treatment.

#4059 MICROBIOLOGICAL ANALYSIS OF HEMODIALYSIS WATER AT THE DOUALA GENERAL HOSPITAL, CAMEROON

Abstract Background and Aims Rigorous control of the microbiological quality of water in hemodialysis services is important because the immune system of patients with chronic renal failure is weakened. The aims of this study was to determine the microbiological quality of water for hemodialysis in Nephrology Unit of the Douala Général Hospital in order to improve the disinfection strategy. Method Twelve water samples were collected each month at different sites of the hemodialysis circuits A (inlet of filters), B (Outlet of filters / inlet of Reverse Osmosis (RO) device) and C (outlet of the RO device / close to the generator) between November 2015 and February 2016 to be analyzed. The bacteria were isolated after filtration of 100 ml of water at each site through nitrocellulose membrane with 0.45 µm microporosity deposited on the surface of the Tryptone Glucose Extract Agar (TGEA) and then incubated at room temperature (20 to 22°C) for 7 days. After transplanting to different environments, pure bacterial isolates were identified by their cultural characters and marketed biochemical galleries. Results The colony count was well above the required international standards (˃100 CFU / ml), for the hemodialysis water with a percentage of 50% of non-compliance. Among the bacteria identified, seven (07) were Gram-negative bacilli including Pseudomonas fluorescens, and Klebsiella pneumoniae subsp ozaenae, three (03) Gram-positive bacilli all Bacillus sp and three (03) Gram-positive cocci all of coagulase-negative staphylococci. The most frequently isolated bacterial genera were Pseudomonas sp (38,5%), Staphylococcus sp (23%), Bacillus sp (23%) and Klebsiella sp (15,5%). Conclusion The high bacteriological contamination of the hemodialysis water with the detection of a variety of bacteria shows that the disinfection procedure of the distribution loop is not efficient and cannot prevent the development of a biofilm. A higher frequency of disinfection (almost every week), an increase of the concentration and time of contact of the chlorine disinfection product or the use of peracetic acid and a regular monitoring can contribute to improve the quality of the hemodialysis water at the Douala General Hospital to ensure a better quality of life for patients undergoing this treatment.

Post-COVID immunopatology syndrome: characteristics of phenotypical changes in the immune system in post-COVID patients

This study examines the long-term effects of SARS-CoV-2 infection on immune status. Given the prolonged and profound immune dysregulation observed during acute SARS-CoV-2 infection, it remains to be determined whether these changes translate into subsequent immune system dysfunction in recovering individuals. In this sense, the aim of the study was to study the parameters of the immune system in patients who had undergone SARS-CoV-2 infection. 150 patients who underwent SARS-CoV-2 infection were examined according to 96 parameters using flow cytometry. A complete blood count was performed using a Medonic device (Sweden); ELISA method determined the levels of general and specific IgM, IgG, IgA, compliment fragments (JSC Vector-Best, Russia). The activity of the phagocytes was studied according to the generally accepted method. The study found that at least four phenotypes of immune system disorders are detected in patients. The first two phenotypes are related to the impairment of innate immune system factors and are associated with a decrease in the number of CD46+ and NK cells. It has been observed that a decrease in CD46+ persists for a long time in a significant number of recovered patients, highlighted by the impaired expression of this marker in various subpopulations of lymphocytes. The decrease in the level of natural killers was accompanied by a compensatory increase in the number of T lymphocytes, mainly due to T helpers and TNK lymphocytes, and the growth of total memory B cells. Two other identified phenotypes are characterized by damage to acquired immune response factors and are associated with damage to B cells and T cytotoxic cells. The relationship of such disorders with damage to hematopoiesis erythrocyte and platelet sprouts, which contribute to the appearance of hypoxia and possible violation of the blood coagulation system, has been shown. Therefore, the results obtained indicate a long-term pronounced damage to the immune system in postCOVID patients that requires immunocorrection of these disorders.

Chimeric Antigen Receptor T-Cell Therapy and Imaging Applications for Large B-Cell Lymphoma

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of large B-cell lymphoma (LBCL) and other hematologic malignancies. Its mechanism of action relies on recent biotechnological advances that allow clinicians to harness and enhance a patient's immune system to fight cancerous cells. The indications for CAR T-cell therapy continue to expand, with ongoing trials evaluating their use in other hematologic and solid organ malignancies. This review explores the vital role of diagnostic imaging in patient selection and treatment response in CAR T-cell therapy for LBCL and the management of specific therapy-related adverse events. For a patient-centered and cost-effective use of CAR T-cell therapy, it is crucial to select patients who are likely to derive long-term benefit and optimize their care during a lengthy treatment pathway. Metabolic tumor volume and kinetics assessed at PET/CT have emerged as powerful tools to predict outcome after CAR T-cell therapy in LBCL, allowing for the early identification of lesions refractory to treatment and identification of the severity of CAR T-cell therapy toxicity. Radiologists should be aware that the success of CAR T-cell therapy is mitigated by adverse events, most importantly neurotoxicity, which remains poorly understood and challenging to treat. Neuroimaging, with experienced clinical evaluation, is critical in the diagnosis and management of neurotoxicity and the exclusion of other central nervous system complications that can occur in this clinically vulnerable patient group. This review discusses current applications of imaging in the standard CAR T-cell therapy pathway for the treatment of LBCL, which serves as a model disease in the integration of diagnostic imaging and radiomic risk markers.