Cell Levels In Patients Research Articles

Effects of Splenectomy on Natural Killer Cell Levels in β-Thalassemia Major Patients.

In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with β-thalassemia major (β-TM). Seventy patients with β-TM (38 splenectomized and 32 nonsplenectomized) and 25 healthy controls were included in this study. The hemogram parameters, ferritin, T lymphocyte, T-helper cell, T-suppressor cell, and NK cell numbers, were measured. The T lymphocyte (CD3+) level was found to be significantly higher in the patient group (p < 0.05). CD3+/CD4+ T lymphocytes were detected to be significantly higher in the patient group (p < 0.05). Although the CD3+/CD4+ T lymphocyte level was significantly higher in the nonsplenectomy group (p < 0.05), this was not the case in the splenectomy group. When the patient and control groups were compared, no significant difference was detected regarding CD3+/CD8+ T lymphocyte levels. CD3-/CD16+CD56+ NK cell level was found to be significantly lower only in the splenectomy group than in the control group (p < 0.05). We found that there was a significant negative correlation between serum ferritin levels and both total lymphocyte (r = -0.617) and CD3+ lymphocyte (r = -0.718) levels in the control group (p < 0.05). A significant negative correlation was detected between serum ferritin levels and CD3-/CD16+CD56+ NK cell levels in the patient group (r = -0.410) (p < 0.05). Splenectomy reduces NK cell levels in patients with β-TM. The negative relationship between ferritin levels and NK cells indicates that ferritin levels should be kept under control in patients with β-TM.

Profil des lymphocytes T CD8+ dans l’eczéma allergique de contact sur peaux pigmentées

ObjectiveTo analyze the levels of CD8+ T cells during the effector phase of allergic contact dermatitis. Patients and methodsThis was a cross-sectional, exposed-unexposed study with several passages. The study included 150 exposed patients and 150 matched unexposed subjects representing the control population. Patch tests were performed in exposed subjects. CD8+ T cell counts were performed by flow cytometry. Each patient received 3 samples (Day 0, Day 2 and Day 4). Only one sample was taken from the controls. We considered the average CD8+ T cell rate of the controls as a reference value. Any value below this level was considered low and any value above it was considered high. ResultsThe mean age was 35.77 years. The main allergens were fragrance mix, nickel sulfate and potassium dichromate. The mean CD8+ T cell level in patients at D0 was significantly higher than in the control population. It increased significantly from D0 to D4. There was a significant relationship between mean CD8+ T cells levels and patch test results. There was a twofold increase in the risk of having an elevated CD8+ T cells level when having allergic contact dermatitis. ConclusionOur study showed significant levels of CD8+ T cell in subjects with allergic contact dermatitis. However, it should be supported by work on the exact nature of hapten-specific effector CD8+ T cells, the cytokines involved and the role played by other potential effector cells in allergic contact dermatitis.

HB-300, a novel arenavirus-based cancer immunotherapy in patients with metastatic castration-resistant prostate cancer.

TPS5108 Background: Prostate cancer is the most frequent type of malignant neoplasia in men. Immunotherapy targeting self-antigens in prostate cancer is evolving and requires overcoming multiple mechanisms that mediate immune tolerance. Sipuleucel-T, a cell-based therapy recognizing prostatic acid phosphatase (PAP) protein, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and induced PAP-specific T cell responses correlating with overall survival (OS). Poxvirus vectors encoding prostate-specific antigen (PSA) increased PSA-specific T cell levels and were associated with OS benefit, although not confirmed in a Phase 3 study. Arenaviral vectors used in preclinical tumor models could overcome self-tolerance by inducing strong self-antigen specific CD8 T cell responses. In humans, arenaviral vectors encoding HPV16 E7E6 fusion protein (HB-200) induced unprecedented E6E7-specific CD8 T cell levels in patients with recurrent/metastatic HPV16+ cancers. Preliminary clinical activity and favorable safety and tolerability were observed in these heavily pre-treated, checkpoint inhibitor-resistant patients (ref: Fu et al. ASCO 2022; NCT04180215). It is therefore hypothesized that HB-300, a live-attenuated arenaviral vector therapy encoding the self-antigens PAP and PSA, will induce substantially stronger T cell responses in prostate cancer patients than previously tested active immunization approaches. Methods: This is a Phase 1/2 open-label clinical study of HB-300 in ~ 70 patients with advanced mCRPC. A 3+3 Dose Escalation will be followed by a dose-expansion to confirm the recommended Phase 2 dose (RP2D). HB-300 consists of HB-302 (Pichinde virus based) alternating with HB-301 (LCMV based) vectors, administered IV every 3 weeks (Q3W) for 5 doses then Q6W. The program’s entry into the clinic with a mini dose-escalation was supported by the submission of a data master file along with the HB-300 Investigational New Drug application, based on arenavirus vector platform data collected in the HB-200 program. Trial inclusion criteria include male participants age ≥ 18; documented mCRPC (adenocarcinoma without neuroendocrine or small cell features); receipt of at least 1 androgen deprivation therapy and no prior chemotherapy regimens (docetaxel in the castration-sensitive setting is allowed); ≥1 measurable lesion; ECOG PS 0-1. Exclusions are uncontrolled pain or symptoms; active auto-immune disease; immunosuppression; active central nervous system or liver metastasis; and active infection. Phase 1 primary objectives include safety/tolerability and determination of RP2D, secondary objectives include preliminary efficacy, and exploratory assessments include antigen-specific T cell response and circulating tumor cell analysis. Clinical trial# NCT05553639. Clinical trial information: NCT05553639 .

MRI histogram analysis of tumor-infiltrating CD8+ T cell levels in patients with glioblastoma

ObjectiveTo investigate the utility of preoperative magnetic resonance imaging histogram analysis for evaluating tumor-infiltrating CD8+ T cells in patients with glioblastoma (GBM). MethodsWe retrospectively analyzed the pathological and imaging data of 61 patients with GBM confirmed by surgery and pathology. Moreover, the levels of tumor-infiltrating CD8+ T cells in tumor tissue samples obtained from the patients were quantified through immunohistochemical staining and evaluated with respect to overall survival. The patients were divided into the high and low CD8 expression groups. Preoperative T1-weighted contrast-enhanced (T1C) histogram parameters of patients with GBM were extracted using Firevoxel software. We investigated the correlation between the histogram feature parameters and CD8+ T cells. We performed statistical analyses of the T1C histogram parameters in both groups and identified characteristic parameters with significant between-group differences. Additionally, we performed a receiver operating characteristic curve (ROC) analysis to determine the predictive utility of these parameters. ResultsThe levels of tumor-infiltrating CD8+ T cells were positively associated with overall survival in patients with GBM (P = 0.0156). Among the T1C histogram features, the mean, 5th, 10th, 25th, and 50th percentiles were negatively correlated with the levels of CD8+ T cells. Moreover, the coefficient of variation (CV) was positively correlated with the levels of CD8+ T cells (all P < 0.05). There was a significant between-group difference in the CV, 1st, 5th, 10th, 25th, and 50th percentiles (all p < 0.05). The ROC curve analysis revealed that the CV had the highest AUC value (0.783; 95% confidence interval: 0.658–0.878), with sensitivity and specificity values of 0.784 and 0.750, respectively, for distinguishing between the groups. ConclusionsThe preoperative T1C histogram have additional value for the levels of tumor-infiltrating CD8+ T cells in patients with GBM.

Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a type 2 helper T-cell (Th2)-mediated allergic disease that involves mast cells. This study aimed to clarify the relationship between perception of symptoms and mast cell levels in patients with EoE. We enrolled patients with asymptomatic esophageal eosinophilia (aEE) and those with symptomatic EoE. Immunofluorescence staining was performed on esophageal biopsy specimens to quantify mast cell-related molecules, such as tryptase, proteinase-activated receptor (PAR)-2, and vasoactive intestinal peptide receptor (VPAC)-1. We evaluated 28 and 58 patients with aEE and EoE, respectively. There were no significant differences in clinical and endoscopic features and peak eosinophil counts between both groups. Mast cell tryptase-positive areas were significantly higher in EoE than in aEE (4.9 [3.5-6.2] vs. 2.0 [1.2-3.4] %, p < 0.01). The number of PAR-2-positive cells was significantly higher in EoE than in aEE (14 [8.8-20.0] vs. 4 [2.8-8.0] cells/high-power field [HPF], p < 0.01). The number of VPAC-1-positive cells was significantly higher in the EoE group than in the aEE group (13 [8.8-16.0] vs. 6 [3.0-9.3] cells/HPF, p < 0.01). A positive correlation was observed between the numbers of PAR-2-positive cells and VPAC-1-positive cells (r = 0.851, p < 0.01). Moreover, mast cell tryptase-positive areas positively correlated with the number of PAR-2- and VPAC-1-positive cells (r = 0.352, p < 0.01; r = 0.355, p < 0.01, respectively). Esophageal mast cells and their receptors, PAR-2 and VPAC-1, may contribute to the perception of symptoms in patients with EoE.

Molecular remission at T cell level in patients with rheumatoid arthritis

While numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

Regulatory B cell imbalance correlates with Tfh expansion in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis, microangiopathy and immune dysfunction. B cell abnormalities characterised by autoantibody production and polyclonal B cell activation play an important role in the pathogenesis of SSc. We previously identified an expansion of functional and activated circulating T follicular helper (cTfh) cells in SSc patients. The aim of this study was to analyse the frequency of regulatory B (Breg) cell subsets and the correlation with Tfh in SSc patients. Circulating Breg cells CD24hiCD38hi and CD27+CD24hi levels and cTfh cells CD4+CXCR5+PD1+ were determined by cytometry in 50 SSc patients and 32 healthy subjects. The frequency of Breg cells CD24hiCD38hi and CD24hiCD27+ was significantly reduced in patients with SSc as compared to controls (p=0.02 and p<0.001, respectively). In contrast, when examining the CD21low B cell subset, the frequency was significantly increased in SSc patients compared to healthy controls, (p<0.001). There was no difference in Breg cell levels in patients with diffuse SSc and limited SSc. However, CD24hiCD27+ Breg cell frequency was significantly decreased in SSc patients with pulmonary arterial hypertension (p=0.014), but not in patients with interstitial lung disease (p=0.058). Furthermore, we observed a negative correlation between cTfh and CD24hiCD27+ Breg cell levels in SSc patients but not in healthy controls (p=0.02). These results suggest that Breg cell subsets may participate in the regulation of cTfh and disease severity. Decreased CD24hiCD27+ Breg cell frequency may contribute to the development of SSc.

The loss of RNA N6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8+ Tcell dysfunction and tumor growth.

Tumor-associated macrophages (TAMs) can dampen the antitumor activity of Tcells, yet the underlying mechanism remains incompletely understood. Here, we show that C1q+ TAMs are regulated by an RNA N6-methyladenosine (m6A) program and modulate tumor-infiltrating CD8+ Tcells by expressing multiple immunomodulatory ligands. Macrophage-specific knockout of an m6A methyltransferase Mettl14 drives CD8+ Tcell differentiation along a dysfunctional trajectory, impairing CD8+ Tcells to eliminate tumors. Mettl14-deficient C1q+ TAMs show a decreased m6A abundance on and a higher level of transcripts of Ebi3, a cytokine subunit. In addition, neutralization of EBI3 leads to reinvigoration of dysfunctional CD8+ Tcells and overcomes immunosuppressive impact in mice. We show that the METTL14-m6A levels are negatively correlated with dysfunctional Tcell levels in patients with colorectal cancer, supporting the clinical relevance of this regulatory pathway. Thus, our study demonstrates how an m6A methyltransferase in TAMs promotes CD8+ Tcell dysfunction and tumor progression.

Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study

BackgroundIn December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients.MethodsIn this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death.ResultsThe main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235–57.671] and CD8+T [HR: 10.883; 95%CI: 3.277–36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients.ConclusionsReductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient’s disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients.Trial registrationPrognostic Factors of Patients With COVID-19, NCT04292964. Registered 03 March 2020. Retrospectively registered.

Mutation location of HCM-causing troponin T mutations defines the degree of myofilament dysfunction in human cardiomyocytes

BackgroundThe clinical outcome of hypertrophic cardiomyopathy patients is not only determined by the disease-causing mutation but influenced by a variety of disease modifiers. Here, we defined the role of the mutation location and the mutant protein dose of the troponin T mutations I79N, R94C and R278C. Methods and resultsWe determined myofilament function after troponin exchange in permeabilized single human cardiomyocytes as well as in cardiac patient samples harboring the R278C mutation. Notably, we found that a small dose of mutant protein is sufficient for the maximal effect on myofilament Ca2+-sensitivity for the I79N and R94C mutation while the mutation location determines the magnitude of this effect. While incorporation of I79N and R94C increased myofilament Ca2+-sensitivity, incorporation of R278C increased Ca2+-sensitivity at low and intermediate dose, while it decreased Ca2+-sensitivity at high dose. All three cTnT mutants showed reduced thin filament binding affinity, which coincided with a relatively low maximal exchange (50.5 ± 5.2%) of mutant troponin complex in cardiomyocytes. In accordance, 32.2 ± 4.0% mutant R278C was found in two patient samples which showed 50.0 ± 3.7% mutant mRNA. In accordance with studies that showed clinical variability in patients with the exact same mutation, we observed variability on the functional single cell level in patients with the R278C mutation. These differences in myofilament properties could not be explained by differences in the amount of mutant protein. ConclusionsUsing troponin exchange in single human cardiomyocytes, we show that TNNT2 mutation-induced changes in myofilament Ca2+-sensitivity depend on mutation location, while all mutants show reduced thin filament binding affinity. The specific mutation-effect observed for R278C could not be translated to myofilament function of cardiomyocytes from patients, and is most likely explained by other (post)-translational troponin modifications. Overall, our studies illustrate that mutation location underlies variability in myofilament Ca2+-sensitivity, while only the R278C mutation shows a highly dose-dependent effect on myofilament function.

Increased Serum Interleukin-2 Levels Are Associated with Abnormal Peripheral Blood Natural Killer Cell Levels in Patients with Active Rheumatoid Arthritis.

Objective To investigate the relationship between serum interleukin-2 (IL-2) levels and disease activity, absolute numbers of peripheral lymphocyte subsets, autoantibodies, and associated cytokines in patients with rheumatoid arthritis (RA). Methods This study included 106 patients with RA, evaluated their disease activity (DAS28 score), and divided them into disease remission (DAS28 ≤ 2.6), low disease activity (DAS28 ≤ 3.2), and moderate-high disease activity (DAS28 > 3.2) groups. Flow cytometry was used to detect the absolute numbers of peripheral lymphocyte subpopulations and CD4+ T cell subsets in each group, and serum cytokine levels were measured using cytometric bead array. Results Serum IL-2 levels in RA patients were positively correlated with disease activity and rheumatoid factor titers (p < 0.001 and p = 0.045, respectively), and multiple regression analysis revealed that serum IL-2 levels were an independent factor affecting disease activity. Serum IL-2 levels were positively correlated with Th17/Treg ratios (p = 0.013). Compared with the remission group, peripheral lymphocyte and CD4+ T lymphocyte subsets in patients with active RA decreased to varying degrees; however, the numbers of peripheral natural killer (NK) cells were significantly higher in the moderate-high disease activity group than in the remission (p = 0.046) and low disease activity (p = 0.020) groups; the percentages of NK cells had the same trend. In addition, the number and percentage of NK cells were positively correlated with serum IL-2 levels (p = 0.018 and p = 0.006, respectively). Conclusions In RA patients, serum IL-2 levels were not only correlated with patients' disease activity and autoantibody levels but were also involved in their Th17/Treg immune imbalance. In addition, in patients with active RA, NK cell levels were abnormally elevated, possibly due to high serum levels of IL-2.

Relationship Between T Regulatory Cell Levels (CD4+, CD25+, CD127- T cells) and the Presence of Autoantibodies in Adult Patients with Selective IgA Deficiency

Aim: Selective immunoglobulin A (sIgA) deficiency is the most common primary immunodeficiency. Individuals with selective IgA deficiency are generally considered to be asymptomatic. In some patients, autoimmune diseases have been reported. Regulatory T cells (T reg) are a group of cells that play a key role in preventing autoimmunity.Material and Methods: 28 patients with selective IgA deficiency and a control group consisting of 15 individuals of similar age and sex were included in the study.Results: Serum IgA levels were lower in patients with sIgA deficiency (p 0.001). There was no difference between the two groups in term of the rate of Treg cells (p: 0.562 and p: 0.873). There was at least one autoantibody positivity in 19 (67.8%) patients with sIgA deficiency and 4 (26.7%) in the control group. The most common positive autoantibody was ANA in both groups. Serum IgG and IgG1 levels were significantly higher in sIgA deficiency patients with autoantibody than in the other group (p: 0.004 and p: 0.004) The relationship between presence of autoantibodies and Treg cell levels in patients with sIgA deficiency was not statistically significant (p: 0.199). The regression analysis showed that the IgG level (OR: 1.594, 95% CI: 1.096-2.319, p: 0.015) was an independent predictor for the presence of autoantibodies.Conclusion: The findings of our study are important as they are the first evaluation in adult sIgA deficient patients. Further studies are required to shed light on this issue in order to evaluate more patients with sIgA deficiency with autoimmunity.

Effects of dasatinib on CD8+T, Th1, and Treg cells in patients with chronic myeloid leukemia.

ObjectiveTo investigate the immunomodulatory effects of the tyrosine kinase inhibitor (TKI) dasatinib on T-cell subtypes in patients with chronic myeloid leukemia (CML).MethodsT helper (Th) 1, Th2, regulatory T (Treg), and CD8+T cell levels were detected in patients with CML (n = 9) before and after dasatinib treatment. The corresponding response level at the time of a blood test was evaluated.ResultsAfter dasatinib treatment, six patients achieved a better response level, while three did not show improved response levels. Among the total nine patients, there were no significant differences in Th1, Th2, and Treg cell levels, whereas CD8+T cell levels were significantly increased after dasatinib treatment compared with before treatment. When we analyzed the six patients who obtained a better response level, Th1 and CD8+T cell levels were significantly increased after dasatinib treatment, but Th2 and Treg cell levels did not change. The other three patients who did not have improved response levels showed decreased Th1 cell levels and increased Treg cell levels after treatment.ConclusionsDasatinib may increase Th1 and CD8+T cell levels, and decrease Treg cell levels in patients with CML. This finding might be associated with a good therapeutic response to this drug.

Prognostic role white blood cell levels in patients with advanced pancreatic adenocarcinoma undergoing first-line chemotherapy

Prognostic role white blood cell levels in patients with advanced pancreatic adenocarcinoma undergoing first-line chemotherapy

The effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells and natural killer cells in patients with chronic hepatitis C.

Currently, hepatitis C antiviral therapy is entering a new era with the use of direct-acting antiviral (DAA) agents. However, the precise immunological influences of DAA therapy in patients with chronic hepatitis C (CHC) are insufficiently understood. This study aimed to investigate the effects of DAA therapy on the frequency of myeloid-derived suppressor cells (MDSCs), T lymphocytes, and natural killer (NK) cells in patients with CHC. Thirty-two treatment-naive CHC patients were treated with DAA therapy, and the frequency of immune cells was analyzed by flow cytometry at various time points during and after therapy. Sixteen healthy donors were recruited for comparison. DAA therapy decreased the frequency of MDSCs and monocytic MDSCs in patients with CHC to a normal level. DAA therapy also increased the CD8+ T and NK cell levels in patients with CHC. In addition, activation (NKp30 and NKp46) and inhibitory (NKG2A) receptors on NK cells were downregulated to yield an NK cell phenotype resembling that observed in the healthy controls. This study provides insight into the normalization of immune cell levels under DAA therapy and indicates that restoration of the immune system in patients with CHC strongly supports long-term curative hepatitis C virus eradication.

Association between echocardiographic epicardial fat thickness and circulating endothelial progenitor cell level in patients with stable angina pectoris.

Epicardial adipose tissue is associated with coronary artery disease (CAD). Circulating endothelial progenitor cell (EPC) level represents a marker of endothelial dysfunction and vascular health. However, the relationship between epicardial fat and circulating EPC remains unknown. This study aimed to investigate association between echocardiographic epicardial fat thickness (EFT) and circulating EPC level. Epicardial fat causes inflammation and contributes to progression of CAD. We enrolled 213 consecutive patients with stable angina, and EFT was determined by echocardiography. Quantification of EPC markers (defined as CD34 + , CD34 + KDR + , CD34 + KDR + CD133 + cells) in peripheral blood samples was used to measure circulating EPCs. All patients were divided into 3 tertiles according to EFT levels: group 1, low tertile of EFT; group 2, middle tertile of EFT; and group 3, high tertile of EFT. Among the 3 groups, CAD disease severity determined by SXscore was negatively correlated with EFT, but the difference did not reach statistical significance (P = 0.066). Additionally, patients in the high and middle tertiles of EFT had higher circulating EPC levels than did those in the low tertile of EFT (P = 0.001 and P < 0.001, respectively). In multivariate analysis, EPC level was significantly associated with echocardiographic EFT (standardized β = -0.233, P = 0.001), independent of multiple covariates. Epicardial adipose tissue is associated with circulating EPC levels. There was a trend between epicardial fat and severity of CAD, though analysis did not reach statistical significance, and this may be attributed to the interaction between several risk factors of CAD.

Decreased IL-10-producing B cell level in patients with pemphigus but not with pemphigoid

Decreased IL-10-producing B cell level in patients with pemphigus but not with pemphigoid

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma.

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.

Correlation between epidermal growth factor receptor tyrosine kinase inhibitor efficacy and circulating tumor cell levels in patients with advanced non-small cell lung cancer.

ObjectiveThe aim of this study was to investigate the correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and circulating tumor cell (CTC) levels in patients with advanced non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs in reducing CTC counts in patients with advanced NSCLC was studied.Patients and methodsA total of 66 patients with advanced NSCLC were enrolled and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients’ median CTC counts. All the patients were treated with an EGFR-TKI, and the treatment efficacy and prognoses were compared.ResultsThe treatment efficacies were 53.3% (16/30) and 27.8% (10/36) for the low CTC group and high CTC group, respectively, and this difference was statistically significant (P<0.05). The median overall survival was 22.8 months (95% confidence interval [CI]: 18.9–26.8 months) for the low CTC group and 18.3 months (95% CI: 2.9–8.2 months) for the high CTC group. The median progression-free survival was 11.5 months (95% CI: 8.1–15 months) and 5.6 months (95% CI: 2.9–8.2 months) for the low and high CTC groups, respectively, and the difference was statistically significant (P<0.05).ConclusionThe CTC count can be used as an index for predicting the EGFR-TKI effect on patients with advanced NSCLC. Efficacy and prognosis of EGFR-TKI treatment and CTC count were considered important, and the CTC count could be used to predict the efficacy of EGFR-TKI treatment and prognosis of advanced NSCLC. The change in CTC expression levels can be used as an index for evaluating the prognosis of patients with advanced NSCLC.

Reduced survival in patients with early-stage non-small-cell lung cancer is associated with high pleural endothelial progenitor cell levels.

Endothelial progenitor cells are capable of contributing to neovascularization in tumours. In patients with either malignant or transudative pleural effusion, we tested the presence of pleural endothelial progenitor cells. We also measured the number of endothelial progenitor cells in post-surgery pleural drainage of either patients with early non-small-cell lung cancer or control patients with benign lung disease undergoing pulmonary resection. The prospective influence of post-surgery pleural-drainage endothelial progenitor cells on cancer recurrence/survival was investigated. Pleural endothelial progenitor cell levels were quantified by fluorescence-activated cell sorting analysis in pleural effusion of 15 patients with late-stage non-small-cell lung cancer with pleural involvement and in 15 control patients with congestive heart failure. Also, pleural-drainage endothelial progenitor cells were measured in pleural-drainage fluid 48 h after surgery in 64 patients with early-stage non-small-cell lung cancer and 20 benign lung disease patients undergoing pulmonary resection. Cancer recurrence and survival was evaluated in patients with high pleural-drainage endothelial progenitor cell levels. The number of pleural endothelial progenitor cells was higher in non-small-cell lung cancer pleural effusion than in transudative pleural effusion. Also, pleural-drainage endothelial progenitor cell levels were higher in patients with non-small-cell lung cancer than in patients with benign lung disease undergoing pulmonary resection (P < 0.05). Non-small-cell lung cancer patients with high pleural-drainage endothelial progenitor cell levels had a significantly 4.9 higher rate of cancer recurrence/death than patients with lower pleural-drainage endothelial progenitor cell levels, irrespective of confounders. Endothelial progenitor cells are present in the pleural effusion and are higher in patients with late-stage non-small-cell lung cancer with pleural involvement than in congestive heart failure patients. Endothelial progenitor cell levels are higher in the post-surgery pleural drainage of patients with non-small-cell lung cancer than in non-neoplastic pleural-drainage fluid. High pleural-drainage endothelial progenitor cell levels in patients undergoing pulmonary resection for early non-small-cell lung cancer predict an increased risk of cancer recurrence and death.