Peripheral Blood Lymphocyte Count Research Articles

Characteristics of cytokines/chemokines associated with disease severity and adverse prognosis in COVID-19 patients

BackgroundCytokines and chemokines as crucial participants in innate immune response play significant roles during SARS-CoV-2 infection, yet excessive immune response exacerbates the severity of COVID-19.PurposeThis study aims to investigate the involvement of which cytokines/chemokines in the cytokine storm of COVID-19, as well as the changes in cytokine/chemokine levels during the course of COVID-19, simultaneously exploring the diagnostic and prognostic value of the relevant cytokines/chemokines for COVID-19.MethodsFlow cytometry was employed to detect the levels of cytokines and chemokines in the serum of 50 COVID-19 patients.ResultsCompared with severe COVID-19 patients, the levels of cytokines IL-6, IL-8, IL-10, sCD25, and chemokines IP-10 and MIG in the peripheral blood of non-severe patients were significantly reduced, while only IL-6, IL-10, and IP-10 levels were significantly decreased compared to non-survivors of COVID-19. Meanwhile, serum concentrations of IP-10, MCP-1, sTREM-1, IL-10, and the neutrophil-to-lymphocyte ratio (NLR) in peripheral blood could distinguish between COVID-19 survivors and non-survivors and were significantly associated with mortality. Among them, the concentration of IP-10 was shown to be the most powerful indicator for predicting adverse outcomes in COVID-19 patients (AUC: 0.715); however, its combined detection with the conventional inflammatory marker NLR did not improve the predictive value for adverse outcomes in COVID-19 patients. Additionally, serum IP-10 levels were negatively correlated with peripheral blood NK cell count and total lymphocyte count, while sTREM-1 levels were positively correlated with peripheral blood CD4+ T cell count and CD3+ T cell count. Meanwhile, IL-8 levels were positively correlated with total lymphocyte count in peripheral blood. Finally, the serum levels of cytokines/chemokines in non-survivors of COVID-19 increased significantly before death, while in survivors, they returned to normal levels before discharge.ConclusionsSeverely ill and non-surviving COVID-19 patients exhibit compromised immune function, with significantly higher levels of inflammation, cytokine/chemokine storms, and immune dysregulation compared to non-severe patients. Serum concentrations of IP-10, MCP-1, sTREM-1, and IL-10 levels can serve as biomarkers to predict adverse outcomes in COVID-19.

Prognostic significance of early nk cell recovery in pediatric t-cell replete allogeneic hematopoietic stem cell transplantation.

Early immune reconstitution, particularly of natural killer (NK) cells with strong graft-versus-leukemia effects, is crucial for the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study examined 122 pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent T-cell replete allo-HSCT at the Children's Hospital of Soochow University from 2019 to 2021. Peripheral blood lymphocyte counts on days 30 and 60 post-transplant were analyzed, focusing on NK cell recovery and its impact on overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, graft-versus-host disease, and CMV reactivation. Patients were categorized into high and low NK cell groups by the median NK cell counts at day 30 (NK30) and day 60 (NK60) after HSCT. Patients with high NK30 and NK60 levels had significantly better 3-year OS rates compared to their respective low NK count groups (86.8% ± 4.7% versus 67.6% ± 7.0%, P = 0.046; 95.7% ± 3.0% versus 63.7% ± 8.7%, P < 0.001, respectively). NK60 was found to be an independent predictor for 3-year OS and RFS in multivariate analysis. Early NK reconstitution was also related to lower NRM rates. However, this correlation disappeared in patients with ALL and those undergoing haploidentical transplantation. In addition, A positive association between early T cell and NK cell reconstitution was found in our study. Higher NK cell counts on days 60 can predict superior OS, RFS and lower NRM in pediatric AML allo-HSCT patients.

Eosinophil-to-Lymphocyte Ratio and Eosinophil Count as New Predictive Markers for Osteoarthritis.

Despite the association between peripheral blood inflammatory biomarkers and a range of inflammatory diseases, the role of these biomarkers in osteoarthritis (OA) progression remains unclear. Additionally, whether alterations in these inflammatory markers impact the prognosis of OA patients remains an understudied area. The aim of our study was to investigate the specific associations between peripheral blood inflammatory markers and OA progression and OA-related mortality. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 through 2018. The primary outcomes were all-cause mortality, cardiac mortality, and renal disease mortality, with information on the corresponding mortality rates for each participant obtained through association with the National Death Index (NDI). Multivariate logistic regression models were used to examine the relationship between peripheral blood lymphocyte counts and OA, and restricted cubic spline (RCS) analysis was utilized to assess whether there was a nonlinear relationship with OA and mortality of OA patients. Interaction and stratified analyses were employed to explore the association between peripheral blood leukocyte counts and OA. This study included 1077 OA patients and 21,612 non-OA participants. In model 3 fully adjusted for covariates, eosinophil-to-lymphocyte ratio (ELR) and eosinophil (EOS) were positive risk factors promoting the development of OA (OR = 3.26, 95% CI: 1.49-7.14; OR = 1.79, 95% CI: 1.12-2.88). In stratified models for age, sex, BMI, smoking status, and alcohol consumption, the associations of ELR and EOS with OA were significantly different. RCS curves showed a J-shaped relationship between ELR and EOS and all-cause mortality in patients with OA. ELR was also found to significantly up-regulate cardiac mortality and renal mortality in patients with OA (OR = 3.92, 95% CI: 1.68-9.14; OR = 22.55, 95% CI: 6.55-77.70), while EOS was only significantly positively correlation (OR = 3.68, 95% CI: 1.94-7.01). A significant relationship was found between ELR, EOS and OA. In addition, ELR and EOS were identified as potential predictors of mortality from different causes in patients with OA.

Evaluating peripheral blood lymphocyte subset composition and lipopolysaccharide-induced cytokine secretory activity in mononuclear leukocyte cultures from patients with febrile and meningeal forms of tick-borne encephalitis

Introduction.Multiple studies on immune response in patients with various clinical forms of tick-borne encephalitis (TBE) have shown conflicting results. The study aim was to estimate the changes in peripheral blood lymphocyte subset counts and activity of spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production in the mononuclear leukocyte cultures in patients with febrile and meningeal acute TBE.Materials and methods.Groups 1 and 2 included 16 and 12 patients with febrile and meningeal acute TBE, respectively. The control group included 13 healthy donors. Hemogram and T-lymphocyte, T-helper cell, T-cytotoxic and NK cell counts were analyzed by flow cytometry at week 1 of the disease as well as the spontaneous and LPS-stimulated secretion levels of TNFα, IL-1β, IL-6, IL-10, IL-8, and MCP-1 were assessed by ELISA in the supernatants of mononuclear cell cultures twice: during hospitalization and two weeks later. Statistical analysis was performed by the Mann–Whitney U-test, and Wilcoxon test.Results.Group 2 demonstrated significant decrease in spontaneous and/or LPS-stimulated levels of proinflammatory cytokines IL-1β, IL-6, MCP-1, and TNFα, but showed higher IL-8 level as compared with Group 1. In addition, spontaneous and/or LPS-induced levels of IL-6 and TNFαin Group 2 did not significantly differ from the controls, which presumably also indicated the suppression of their production. In contrast, spontaneous and/or LPS-induced levels of IL-1β, IL-6, MCP-1, and TNFαin Group 1 were higher than in the controls. The spontaneous IL-10 level in the patients from both groups were higher than in the controls. Peripheral blood lymphocyte and T-cytotoxic T-lymphocyte counts in both groups of TBE patients were lower than in the controls. There was significant increase in neutrophil counts, decrease in NK cell count in Group 2 as compared to the patients with a milder febrile form.Conclusion.Meningeal acute TBE patients was presumably associated with inadequate immune response with NK cell deficiency, T-cell dysfunction, increased neutrophil count in the peripheral blood and impaired pro-inflammatory cytokine production related to innate immune response.

Analysis of characteristics of peripheral blood lymphocytes in endometrial carcinoma: a single-center study based on five-year clinical data

IntroductionThis study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs’ clinical application value.MethodsThis single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann–Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test.ResultsThe immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group.ConclusionsWith the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC.Trial registrationThis study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Clinical Factors Influencing the Radiation Dose of Circulating Immune Cells during Radiotherapy for Small Cell Lung Cancer.

Small cell lung cancer (SCLC) has garnered significant attention due to its high malignancy, propensity for distant metastasis, and poor prognosis. Radiotherapy remains the cornerstone of treatment for limited-stage small cell lung cancer (LS-SCLC). However, outcomes with radiotherapy alone or in combination with chemotherapy remain suboptimal. Radiotherapy can induce lymphopenia by directly irradiating hematopoietic organs or destroying mature circulating lymphocytes, leading to immunosuppression and consequently diminishing therapeutic efficacy. The estimated dose of radiation to immune cells (EDRIC) model integrates factors such as hemodynamics, lymphocyte radiosensitivity, and proliferation capacity. This study employs the EDRIC model with enhancements to calculate the circulating immune cell radiation dose. By utilizing the EDRIC methodology, the study explores the correlation between EDRIC and tumor target size, average lung dose, average heart dose, clinical features, and peripheral blood lymphocytopenia during radiotherapy for LS-SCLC, aiming to inform personalized patient treatment strategies. This study analyzed data from 64 LS-SCLC patients who met the inclusion criteria at the General Hospital of Ningxia Medical University from January 2023 to January 2024, all of whom received radical thoracic conventional fractionated radiotherapy. Lymphocyte counts were recorded at the following points: before radiotherapy, at the lowest observed value during radiotherapy, at the end of radiotherapy, and one-month post-radiotherapy. Dosimetric data, including average lung, heart, and body doses, were extracted from the treatment planning system, and the circulating EDRIC was calculated using this model. The relationship between EDRIC values and therapeutic outcomes was analyzed. In LS-SCLC, the EDRIC model effectively predicts lymphocyte count reduction, correlating with planning target volume (PTV; cm3), TNM stage, and the percentage of target lesion shrinkage. Post-radiotherapy, there was a significant decrease in peripheral blood lymphocyte counts, with greater EDRIC values indicating more pronounced lymphocyte reduction.

AB032. The effect of high-dose dexamethasone on systemic immune-inflammation index (SII) in patients with brain tumor, a retrospective study in tertiary hospital in Indonesia.

Inflammation plays an important role in proliferation, migration, and invasion of tumor cells; therefore, many research has been done to investigate inflammation parameters including systemic immune-inflammatory index (SII). Dexamethasone, a strong anti-inflammatory, is still widely used as the main treatment in vasogenic edema. High-dose administration (16 mg/day) is recommended in patients with brain tumors with increased intracranial pressure. We performed this retrospective study to determine SII profile, dexamethasone use, and the effect of high-dose dexamethasone on SII in patients with brain tumors. We performed a retrospective study on patients with brain tumors in 2022-2023 period who were treated with intravenous high-dose dexamethasone. Patient demographics, clinical characteristics of the brain tumor, concurrent infection, as well as dexamethasone dose and duration were recorded. Platelet, neutrophil, and lymphocyte count obtained prior to dexamethasone administration, and on the fifth to seventh day were also collected. SII was calculated by the following formula: neutrophil × platelet counts/lymphocyte. Data were then analyzed using Microsoft Excel 2019 and SPSS 29.0.2.0. We enrolled 56 patients with brain tumors, age 47±13.5 years, 78.6% were female, 69.6% had malignant brain tumors (brain metastases and high-grade primary brain tumors) and 26.8% had concurrent infection. High-dose dexamethasone was administered with average dose of 16.8±3.3 mg/day for average duration of 4.8±1.8 days. SII was significantly higher in malignant compared to benign brain tumors both in prior and after dexamethasone administration (P=0.02, P=0.01). SII was significantly higher in metastasis brain tumor compared to primary brain tumor (P=0.005). High-dose dexamethasone significantly increased SII and decreased lymphocyte count (P=0.006, P=0.04). SII was found higher in malignant brain tumor and brain metastasis. High-dose dexamethasone was administered with average dose of 16.81±3.37 mg/day for average duration of 4.78±1.84 days. SII was found to be higher after high-dose dexamethasone, due to a decrease of lymphocyte counts in peripheral blood.

Prognostic Value of the Controlling Nutritional Status (CONUT) Score in Patients Who Underwent Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy.

The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0-3) and high (4-12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014-5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066-4.547, p = 0.033). These results underscore the CONUT score's effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification.

Antimelanoma differentiation antigen 5-positive dermatomyositis: an update.

Antimelanoma differentiation antigen 5-dermatomyositis (MDA5-DM) is a complex and serious systemic autoimmune disease that primarily affects the skin and lungs. In this review, we aimed to provide new insights into the clinical features, pathogenesis, and practical management approach for this disease. Although lung lesions are prominent in most patients with MDA5-DM, they are now recognized as heterogeneous diseases. Peripheral blood lymphocyte count can serve as a simple and reliable laboratory parameter for categorizing MDA5-DM into three subgroups: mild, medium, and severe. Recent studies have implicated viral infection, genetic factors, autoimmunity against MDA5, multiple immune cells, and interferons as significant contributors to MDA5-DM pathogenesis. In addition to traditional treatments with glucocorticoids and immunosuppressants, many new approaches, including new biologics and targeted agents, have been explored. Additionally, infection is a common complication of MDA5-DM, and prophylaxis or treatment of the infection is as important as treating the primary disease. Knowledge of clinical characteristics and pathogenesis of MDA5-DM has grown in recent years. Although many new therapeutic approaches have been explored, further studies are required to confirm their efficacy.

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

Comparative Analysis of Lymphocyte Populations in Post-COVID-19 Condition and COVID-19 Convalescent Individuals.

Reduced lymphocyte counts in peripheral blood are one of the most common observations in acute phases of viral infections. Although many studies have already examined the impact of immune (dys)regulation during SARS-CoV-2 infection, there are still uncertainties about the long-term consequences for lymphocyte homeostasis. Furthermore, as persistent cellular aberrations have been described following other viral infections, patients with "Post-COVID-19 Condition" (PCC) may present similarly. In order to investigate cellular changes in the adaptive immune system, we performed a retrospective analysis of flow cytometric data from lymphocyte subpopulations in 106 patients with confirmed SARS-CoV-2 infection who received medical care at our institution. The patients were divided into three groups according to the follow-up date; laboratory analyses of COVID-19 patients were compared with 28 unexposed healthy controls. Regarding B lymphocyte subsets, levels of IgA + CD27+, IgG + CD27+, IgM + CD27- and switched B cells were significantly reduced at the last follow-up compared to unexposed healthy controls (UHC). Of the 106 COVID-19 patients, 56 were clinically classified as featuring PCC. Significant differences between PCC and COVID-19 convalescents compared to UHC were observed in T helper cells and class-switched B cells. However, we did not detect specific or long-lasting immune cellular changes in PCC compared to the non-post-COVID-19 condition.

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies.

Interstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS). Here, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately. Peripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS. Patients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD.

Measurement of proviral load associated with the development of lymphocytosis in bovine leukaemia virus‐infected Holstein cattle at a dairy farm in Japan

AbstractWe monitored the bovine leukaemia virus (BLV) proviral load (PVL) in peripheral blood lymphocytes (PBLs) and the PBL counts in BLV‐infected cattle on a dairy farm in Japan to determine the changes in PVL with the progression of lymphocytosis. A total of 25 BLV‐infected Holstein cattle at a dairy farm were followed up from May 2015 (0 month) to April 2016 (11 months). PBL counts and PVL were measured three times in 25 cattle. Based on their PBL counts, five cattle with normal PBL (≤7500 cells/µL) at 0 month but high PBL (&gt;7500 cells/µL) at 11 months were classified as the increased group. All cattle in the increased group showed increased PVL compared to asymptomatic aleukaemic carriers at 11 months. This study revealed increases in PVL with the progression of lymphocytosis, suggesting that cattle with progression of lymphocytosis should be segregated from BLV‐negative cattle as soon as possible.

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS).&#x0D; The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy.&#x0D; Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes.&#x0D; Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses.&#x0D; Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.

Assessment of Immune Status in Patients with Mismatch Repair Deficiency Endometrial Cancer.

This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation. Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann-Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC. Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d. Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.

Abstract 4996: Analysis of the effect of eribulin on tumor immunity against triple-negative breast cancer

Abstract Purpose: Chemotherapeutic agents may induce immunomodulatory effects on immune cells and cancer cells in patients with triple negative breast cancer (TNBC). Recent studies have demonstrated that absolute lymphocyte count in peripheral blood can predict response to eribulin in patients with breast cancer, suggesting that eribulin have some favorable effects on immune cells. However, there have been no reports demonstrating the mechanisms of how eribulin affects the immune cells of patients with breast cancer. This study aimed to analyze the effect of eribulin on T cells in vitro and in vivo. Materials &amp; Methods: Using human peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with TNBC, we investigated the effects of eribulin on proliferation of these cells, changes in the expression of surface markers, and antitumor effects on TNBC cells. Three TNBC cell lines (MDA-MB-231, Hs578T, MDA-MB-157) were used in this study. Human PBMCs were activated by CD3/CD28 stimulation in vitro for six days and analyzed for T-cell surface markers by flow cytometry. For three patients with TNBC who underwent eribulin treatment, blood was collected at baseline and on days 8, 22, and 64 after treatment, and PBMCs were isolated, and analyzed by flow cytometry. Results: The proliferation of activated CD8+ T cells from healthy donors and patients was facilitated when cultured with 1nM of eribulin compared to the control. Moreover, eribulin significantly decreased CD4/8 ratio in T cells (p&amp;lt; 0.05). In PBMCs from healthy donors, the frequency of CD45RA+ CD45RO- cells and CCR7+ cells in CD8+ T cells was significantly increased by eribulin treatment (p&amp;lt; 0.05). Furthermore, eribulin significantly increased CD127+ KLRG1- cells (memory precursor effector cells) and TCF1+ cells in CD8+ T cells (p&amp;lt; 0.01). Furthermore, the anti-tumor effect of activated T cells from PBMCs of healthy donors and patients with TNBC was enhanced when cultured with eribulin in all three TNBC cell lines compared to control, and IFNγ+ CD8+ T cells were significantly increased by eribulin treatment (p&amp;lt; 0.05). However, in TNBC patients treated with eribulin in clinical practice, there were no significant changes in the CD4/8 ratio, the frequency of CD45RA+ cells or CCR7+ cells in CD8+ T cells before and after treatment of eribulin. Conclusions: Our findings suggest that eribulin can facilitate the proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells in vitro. Further analysis of the effects of eribulin on TNBC cells and immune cells in vivo is required, and we continue to analyze immunomodulation in patients treated with eribulin. Citation Format: Shimizu Tadafumi, Takaaki Oba, Ken-ichi Ito. Analysis of the effect of eribulin on tumor immunity against triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4996.

Association between systemic immune-inflammation index and psoriasis: a population-based study.

The systemic immune-inflammation index (SII),as measured by lymphocyte, neutrophil and platelet counts in peripheral blood, is regarded as a favorable indicator of both inflammatory state and immune response. Psoriasis is an immune-mediated disease notable for its chronic inflammation of the entire system. Our research sought to explore the latent link between psoriasis and SII. We performed a cross-sectional investigation utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES, 2009-2014). Employing multivariate linear regression models and subgroup analysis, we sought to uncover the association between SII and psoriasis. This study enrolled a total of 17,913 participants as part of its research cohort. Our multivariate linear regression analysis revealed a notable and positive correlation between SII and psoriasis [1.013 (1.000, 1.026)]. As SII tertiles increased, the risk of psoriasis demonstrated an upward trend. The significant dependence on this positive association were maintained in women, BMI(≥ 30 kg/m2),non-stroke and non-cancer subjects in subgroup analysis and interaction tests. Furthermore, we identified a significant association between SII and psoriasis, characterized by two consecutive inverted U-shaped patterns. Notably, the analysis revealed the most prominent inflection point at a specific value of 797.067. The results indicate a significant correlation between elevated SII levels and the presence of psoriasis. However, to corroborate and strengthen these results, additional large-scale prospective studies are required.

Construction and Validation of a Nomogram Model to Predict the Severity of Mycoplasma pneumoniae Pneumonia in Children.

This study aimed to develop a nomogram model for early prediction of the severe Mycoplasma pneumoniae pneumonia (MPP) in children. A retrospective analysis was conducted on children with MPP, classifying them into severe and general MPP groups. The risk factors for severe MPP were identified using Logistic Stepwise Regression Analysis, followed by Multivariate Regression Analysis to construct the nomogram model. The model's discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer-Lemeshow goodness-of-fit test. Univariate analysis revealed that age, duration of fever, length of hospital-stay, decreased sounds of breathing, respiratory rate, hypokalemia, and incidence of co-infection were significantly different between severe and general MPP. Significant differences (p < 0.05) were also observed in C-reactive protein, procalcitonin, peripheral blood lymphocyte count, neutrophil-to-lymphocyte ratio, ferritin, lactate dehydrogenase, alanine aminotransferase, interleukin-6, immunoglobulin A, and CD4+ T cells between the two groups. Logistic Stepwise Regression Analysis showed that age, decreased sounds of breathing, respiratory rate, duration of fever (OR = 1.131; 95% CI: 1.060-1.207), length of hospital-stay (OR = 1.415; 95% CI: 1.287-1.555), incidence of co-infection (OR = 1.480; 95% CI: 1.001-2.189), ferritin level (OR = 1.003; 95% CI: 1.001-1.006), and LDH level (OR = 1.003; 95% CI: 1.001-1.005) were identified as risk factors for the development of severe MPP (p < 0.05 in all). The above factors were applied in constructing a nomogram model that was subsequently tested with 0.862 of the area under the ROC curve. Age, decreased sound of breathing, respiratory rate, duration of fever, length of hospital-stay, co-infection with other pathogen(s), ferritin level, and LDH level were the significant contributors for the establishment of a nomogram model to predict the severity of MPP in children.

The effect of Phytopaj ) Ferula assa-foetida L. oleo gum resin and tragacanth( in patients with COVID-19: A randomized clinical trial.

Exogenous hydrogen sulfide (H2S) has a positive effect on respiratory diseases. Oleo-gum of Ferula assa-foetida contains this compound. This study assessed the effects of Ferula assa-foetida L. oleo gum resin and tragacanth (Phytopaj) on patients with COVID-19. A randomized, single-blinded, controlled trial (RCT) phase 2 was conducted in Mashhad on hospitalized COVID-19 patients. In this RCT, 122 patients were randomly assigned to either receive a 14-day oral phytopaj plus ordinary treatment or ordinary treatment only. Changes in peripheral blood lymphocyte count (LC) and blood oxygen saturation (PO2) were the endpoints. Mean±SD of PO2 in Phytopaj comparison ordinary treatment before intervention was 91.86±4.62 and 91.41±9.18, after the intervention it was 93.22±4.26 and 91.91±5.92 mmHg; before intervention, mean±SD of peripheral blood lymphocyte count was 1015.90±500.55, and 1104.28±543.61, and after intervention, it was 1652.27±921.38 and 1326.12±719.28/μL respectively. Phyopaj is most useful in moderate stages of Covid19, and it is not recommended for elderly patients and patients with comorbidity until more insight is gained.

Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy

The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.