Immune Markers In Patients Research Articles

Features of the spectrum of immune markers in patients with juvenile depression with clinically high risk of psychosis

IntroductionIdentification of biomarkers associated with the risk of psychosis manifestation in juvenile patients with depression may contribute to a better understanding of the pathogenesis of mental disorders and early diagnosis.ObjectivesTo determine the level of pro-inflammatory and anti-inflammatory cytokines and other inflammatory indicators in the plasma of juvenile patients with depression and clinically high risk of psychosis, and to study the correlation of these markers with the severity of psychopathologic symptoms.Methods80 young men aged 16-24 years with the first depressive episode (F32.1-2, F32.38, F32.8) were examined. Based on the severity of attenuated psychotic symptoms (APS) in the structure of depression according to the SOPS scale, all patients were divided into two groups - with clinically high risk of psychosis (n=58) and with depression without APS (n=22). The HDRS-21 and SANS scales were also used for psychometric assessment. Serum level of cytokines TNF-α, IL-6, IL-8, IL-10, TNF-α/IL-6 ratio, TNF-α/IL-10 ratio, leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, C-reactive protein (CRP) concentration, and the level of autoantibodies to S-100B protein were determined.ResultsBoth groups of patients showed a high level of inflammation assessed by LE and α1-PI activity (p>0.05). Significantly higher level of IL-6 (p=0.03), CRP concentration (p=0.026) and TNF-α/IL-10 ratio (p=0.032) were found in patients with clinically high risk of psychosis. This group was also characterised by high level of autoantibodies to the S-100B protein compared to patients with depression without APS (p=0.048). In the high clinical risk group, correlations were found between the SOPS positive subscale score and the level of TNF-α (R=0.32, p=0.017), IL-8 (R=-0.3, p=0.034), TNF-α/IL-6 ratio (R=0.30, p=0.021) and TNF-α/IL-10 ratio (R=0.32, p=0.014). The SOPS negative subscale score correlated with CRP concentration (R=0.3, p=0.043). The SOPS total score correlated with TNF-α/IL-10 ratio (R=0.31, p=0.021). In this group of patients, the level of IL-10 was found to correlate with the duration of the disease (R=0.48, p<0.001). In patients with depression without APS, the level of IL-6 was correlated with the severity of depression according to the HDRS scale, and the level of TNF-α was associated with the duration of the depressive episode (R=0.51, p=0.029).ConclusionsThe obtained results confirm the involvement of inflammation in the development of juvenile depression. Qualitative and quantitative characteristics of the spectrum of immune markers and the cytokine profile, and correlations with the severity of psychopathologic symptoms were revealed in patients with clinically high risk of psychosis.Disclosure of InterestNone Declared

Immunological predictors of rhythmic transcranial magnetic stimulation (rTMS) efficiency in patients with treatment-resistant schizophrenia

IntroductionModel and clinical studies demonstrate the efficiency of rhythmic transcranial magnetic stimulation (rTMS) in diseases associated with neuroinflammation. The therapeutic potential of rTMS is related to modulation of neuroplasticity in the CNS, activation of neurogenesis and reduction of neuroinflammatory processes. Presumably, one of the factors that determines the efficiency of rTMS can be the features of the immune status of patients.ObjectivesTo reveal the features of the spectrum of inflammatory markers in patients with treatment-resistant schizophrenia with different efficiency of rTMS.Methods 31 male patients aged 16 to 47 years (mean age 29.9 ± 8.4 years) with treatment-resistant schizophrenia who developed a first psychotic episode in adolescence (19-25 years) were examined. The course of rTMS was conducted for 3 weeks (15 sessions). Depending on the dynamics of clinical and psychometric parameters after the course of rTMS, the patients were divided into three groups: group 1 - with worsening of clinical condition (n=8); group 2 - without therapeutic effect (n=12); group 3 - with good therapeutic response (n=11). Before rTMS, leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, and the levels of autoantibodies to S-100B protein and myelin basic protein (MBP) in the plasma of patients were determined. The parameters of 18 healthy male donors without clinical signs of psychiatric and somatic pathology were used as controls.ResultsAll groups of patients were characterised by moderate and high levels of immune system activation, determined by a complex of inflammatory and autoimmune markers. At the same time, the high level of immune system activation in patients with low MTR efficiency was associated with low LE activity in plasma (within the reference range or below the lower limit - 200.6 (168.5- 220.3) nmol/min·mL), which was not consistent with the overall level of inflammation. This group of patients also showed high levels of antibodies to MBP compared to control values (p<0.05). The low LE activity can be explained by the transmigration of neutrophils from the blood to the brain due to a critical increase in the permeability of the blood-brain barrier, which is largely controlled by LE.ConclusionsThe study confirmed the participation of immune mechanisms in the formation of therapeutic resistance in schizophrenia and revealed the characteristics of the spectrum of immune markers in patients with low efficiency of rTMS.Disclosure of InterestNone Declared

Cross-sectional association between systemic metal concentrations and immune markers in patients with total joint arthroplasty.

Total joint arthroplasty (TJA) implants are composed of metal components. Although they are regarded safe, the long-term immunological effects of chronic exposure to the specific implant materials are unknown. We recruited 115 hip and/or knee TJA patients (mean age 68 years) who provided a blood draw for measurement of chromium, cobalt, titanium concentrations, inflammatory markers and systemic distribution of immune cells. We examined differences between the immune markers and the systemic concentrations of chromium, cobalt and titanium. CD66-b neutrophils, early natural killer cells (NK), and eosinophils were present in higher percentages in patients with chromium and cobalt concentrations greater than the median. The opposite pattern was observed with titanium where the percentages of CD66-b neutrophils, early NK, and eosinophils were higher in patients with undetectable titanium. Cobalt concentrations were positively correlated with a higher percentage of gamma delta T cells. Both chromium and cobalt concentrations were positively correlated with higher percentages of plasmablasts. Titanium concentrations were positively correlated with higher CD4 effector memory T cells, regulatory T cell count and Th1 CD4 helper cells. In this exploratory study, we observed altered distribution of immune cells in TJA patients with elevated systemic metal concentrations. Although these correlations were not strong, these exploratory findings warrant further investigation into the role of increased metals circulating in blood and its role in immune modulation.

Interleukin 18 and interleukin 22 as important immune markers in patients with tuberculosis

Tuberculosis (TB) is a lung infection caused by the bacterium Mycobacterium tuberculosis (MTB). TB is a leading cause of death globally, accounting for approximately 1.5 million deaths per year. The aim of this article was to evaluate the immunological role of Interleukin (IL) 18 and Interleukin 22 in patients infected with MTB and multi-drug resistant tuberculosis MDRTB. A total of 182 individuals suspected with MTB admitted to the tuberculosis center in AL-Najaf City, Iraq. A sputum acid-fast stain was performed for each individual and GeneXpert® heminested real time PCR has been performed for MDRTB detection. The two Interleukins was measurement in serum of infected individual using ELISA technique. Out of 182 individuals, there were 20 infected with MTB and 15 infected with MDRTB. Serum IL18 and IL22 levels were significantly elevated (P<0.05) in patients with MTB and MDRTB groups as compared with control subjects. The MDRTB group showed higher serum IL18 and IL22 levels (P<0.05) than the MTB group. This study showed that IL18 and IL22 had a relationship with MTB and might be used to help diagnose TB; Clinical diagnosis of TB may be aided by these tests.

CD4 and CD20 as important immune markers in patients with pulmonary tuberculosis

Tuberculosis (TB) is a serious lung infection caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) is highly contagious, and can be spread through the air from an infected person to others. The aim of this article was to evaluate the immunological role of CD4 and CD20 in patients infected with M. tuberculosis and multi-drug resistant tuberculosis (MDRTB). A total of 182 individuals suspected with M. tuberculosis admitted to the tuberculosis center in AL-Najaf City, Iraq. A sputum acid-fast stain was performed for each individual and GeneXpert® heminested real time PCR has been performed for MDR-M. tuberculosis detection. CD4 and CD20 have been measurement in serum of infected individual using ELISA technique. Serum CD4 and CD20 levels were significantly elevated (P<0.05) in patients with M. tuberculosis and MDR-M. tuberculosis groups as compared with control subjects. The MDRTB group showed higher serum CD4 and CD20 levels (P<0.05) than the M. tuberculosis group. This study showed that CD4 and CD20 had a relationship with M. tuberculosis and might be used to help diagnose TB.

Non-surgical periodontal debridement affects subgingival bacterial diversity in patients with HIV-1 and periodontitis.

Following human immunodeficiency virus-1 (HIV-1) infection and antiretroviral therapy, the development of periodontal disease was shown to be favored. However, the influence of HIV-1 infection on the periodontal microbiota after non-surgical periodontal debridement (NSPD) needs a broad comprehension. This work aimed to compare the subgingival microbiological content of patients infected with HIV-1 and controls (non-infected) with periodontitis undergoing NSPD. The bacterial profile of subgingival biofilm samples of patients with HIV-1 (n=18) and controls (n=14) with periodontitis was assessed using 16S rRNA gene sequencing. The samples were collected at baseline, 30, and 90 days after NSPD. The taxonomic analysis of gingival microbiota was performed using a ribosomal RNA database. The microbiota content was evaluated in the light of CD4 cell count and viral load. Both HIV and control groups showed similar stages and grades of periodontitis. At baseline, the HIV group showed higher alpha diversity for both healthy and periodontal sites. Streptococcus, Fusobacterium, Veillonella and Prevotella were the predominant bacterial genera. A low abundance of periodontopathogenic bacteria was observed, and the NSPD induced shifts in the subgingival biofilm of patients with HIV-1, leading to a microbiota similar to that of controls. Different subgingival microbiota profiles were identified-a less diverse microbiota was found in patients infected with HIV-1, in contrast to a more diverse microbiota in controls. NSPD caused changes in the microbiota of both groups, with a greater impact on the HIV group, leading to a decrease in alpha diversity, and produced a positive impact on the serological immune markers in patients infected with HIV-1. Control of periodontitis should be included as part of an oral primary care, providing the oral health benefits and better control of HIV-1 infection.

Immunological role of cluster of differentiation 56 and cluster of differentiation 19 in patients infected with mycobacterium tuberculosis in Iraq

Tuberculosis (TB) is one of the most dangerous infection mainly caused by gram positive bacteria Mycobacterium tuberculosis (Mtb) and cause many deaths every year worldwide especially in developing countries and activate the humoral and cellular immune response. The aim of this study was to investigate the role of CD56 and CD19 as diagnostic and immune markers in patients infected with Mtb. A total number of 26 patients infected Mtb and 27 patients infected with Multi-Drug resistance Mtb (MDR-Mtb) and 30 healthy individuals were included in this study. Mtb has been diagnosed by acid fast stain and MDR-Mtb were diagnosed by GeneXpert® heminested real time PCR for simultaneous detection of Mtb and rifampicin (RIF) resistance as MDR-Mtb. Serum concentration of CD56 and CD19 has been measurement by Enzyme-Linked Immune-sorbent Assay (ELISA) method. Results of this study showed a significant increase in the serum concentration of CD56 (P value = 0.0001) in Mtb-patients (1.95 ± 0.08 ng/ml) as compared with healthy individuals (1.17 ± 0.09 ng/ml). The same significant increases in the serum concentration of CD56 (2.24 ± 0.12 ng/ml) was reported in MDR-Mtb patients as compared to the healthy individuals. On the other hand, there was significant increase (P value 0.003) in serum concentration of CD19 in Mtb-patients as compared with MDR-Mtb-patients. Results of the study can be concluded that Mtb and MDR-Mtb infection stimulates the cellular and humoral immune response which resulted in the increased production of CD56 and CD19.

Analysis of immune biomarkers in cancer patients with solid tumors versus healthy subjects

Abstract Cytokines and other immune regulatory molecules are critical players in the immune response against cancer. There is growing interest in testing the potential utility of systemic immune biomarkers to track cancer progression and to use them as predictors of effective responses to cancer therapy. The central hypothesis guiding this project is that specific immune biomarkers will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. The objective of this study was to establish baseline of immune markers in patients already started treatment with immunotherapy (n=10) (T), patients starting, but not yet treated (S) with immunotherapy (n=10) and subjects without diagnosed malignant disease (W) (n=10). Blood was collected and plasma was isolated and used in the biomarker (100 markers) analysis using a protein microarray method (RayBiotech). The biomarkers in the three groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on p value, and Significance Analysis of Microarrays (SAM). Although 15 biomarkers were significantly different between S vs. W groups, based on SAM, only seven were found differentially expressed. Similarly, although 10 biomarkers were significantly different between T vs. W groups, based on SAM, only one biomarker was found differentially expressed. Furthermore, SAM revealed that responders (n=4) vs. stable (n=5) subgroup of patients within the T group exhibited 22 differentially expressed biomarkers. Future larger studies will be needed to evaluate whether immune markers will be able to predict effective vs. ineffective responses to immunotherapy and whether they may have therapeutic potential.

Study Correlation between Some Immune Markers in Patients with Lichen Planus: Review Article

Lichen planus is an autoimmune disorder that primarily affects the body's skin and multiple mucous membranes. In multicellular species, protein 53 and syndecan-1protein play an significant role since they control the cell cycle and thus play a major role in tumor suppression and cancer prevention. The p53 gene was therefore identified as a "genome protector," referring to its role in preserving the integrity of genetic information by preventing gene mutations. The purpose of this analysis was to study the association between certain immune markers in lichen planus patients. The aim of this study: Study correlation between some immune markers in patients with lichen planus.
 Methods: 'Thirty formalin-fixed, paraffin-embedded tissue pieces, diagnosed as Oral Lichen planus (OLP), were included in the sample of this report.
 Results: Evaluation of P53 Immunohistochemistry and Evaluation of syndecan-1protein Immunohistochemistry
 Conclusion: The marker p53 expression is high in the patient with Lichen Planus while the second studed markersyndecan-1 protein is less than marker p53.

An explorative study on energy balance in patients with head and neck cancer

Background: Involuntary body weight loss in head and neck cancer is common. Fundamental for weight loss is an energy imbalance where total energy expenditure exceeds energy intake.Aim: To map energy intake and parameters of energy expenditure at the start of and after radiotherapy, and their relation to weight change, body mass index, and immune markers in patients with head and neck cancer.Materials and Methods: Data from 20 patients on energy intake (24-hour dietary intake recalls), total energy expenditure (SenseWear Armband Pro3), resting energy expenditure (indirect calorimetry), body weight, body mass index, and immune markers in serum (C-reactive protein and Interleukin-6) were collected at the start of and after radiotherapy (median 8 mo, range 5–13).Results: No statistical significance was shown between the two measurement points for energy intake or for the different parameters of energy expenditure. Median values for energy balance were 0.93 and 0.96 for the start of treatment and follow-up, respectively. Twelve and 13 patients had a negative energy balance at the start of radiotherapy and at follow-up, respectively.Conclusion: A negative energy balance was seen for the majority of patients, which stresses the importance of nutritional treatment at the start of and after radiotherapy.

The impact of an integrated health-system specialty pharmacy on HIV antiretroviral therapy adherence, viral suppression and CD4 count in an outpatient ID clinic

Background: Atrium Health (AH) is a Charlotte-based not for profit hospital network that currently cares for HIV-infected patients through three outpatient ID clinics. AH recognized that novel approaches to patient care which incorporate clinical pharmacists and health-system specialty pharmacy into the practice model can help improve the HIV continuum. As a result, AH created an HIV specialty pharmacy service line that embedded an HIV-trained clinical pharmacist and pharmacy technician within one of three health-system outpatient ID clinics. Aims: This study aimed to evaluate the antiretroviral medication adherence rate, viral load, and CD4 count among patients utilizing Atrium Health Specialty Pharmacy Service (AH SPS) compared to patients that opted out of the program. Methods: This was a single-center, retrospective cohort study conducted from 7 August 2017 to 30 June 2018. All patients were already on HIV therapy at either entry or declination to the AH SPS program. The intervention group was defined as HIV patient care that incorporated AH SPS into the practice model. The control group was defined as HIV patient care that did not involve our health-system specialty pharmacy. The primary endpoints were medication adherence, viral suppression, and CD4 counts. Adherence was measured using pharmacy claims data and the Medication Possession Ratio (MPR) calculation. Baseline viral load and CD4 count at the time of entry or declination to the program was recorded as well as at the end of the observation period. Comparisons between the opt-in and opt-out groups were made. Results: For those patients using AH SPS, the overall average adherence rate was 100% versus only 89% for those patients that opted out of the service (p < 0.01). Furthermore, all but 3 patients using AH SPS reached viral suppression (p = 0.03) and all but one had improved immunefunction with a CD4 count 200 or greater by the end of the observation period (p = 0.03). The change in viral suppression and CD4 count of 200 or greater was not statistically improved between baseline and follow up in those opting out of using AH SPS. Conclusions: The AH SPS utilized an innovative practice model that fully integrated a specialty pharmacy team within an outpatient ID clinic. This novel approach to patient care significantly improved adherence which in turn lead to improved viral suppression and immune markers in patients enrolled within the program compared to those opting out.

Stability of peripheral blood immune markers in patients with asthma

BackgroundAsthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease.MethodsNineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0.ResultsFEV1 (% predicted), FEV1/FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor.ConclusionAmong the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

Determining Prognostic Immune Markers in Patients With Ovarian Cancer

Determining Prognostic Immune Markers in Patients With Ovarian Cancer

Defining the Immune Checkpoint Landscape in the Bone Marrow and Peripheral Blood of Patients with Chronic Lymphocytic Leukemia (CLL)

Background: Limited data is available on expression levels of checkpoint receptors, respective ligands, and other immune markers in patients with CLL (Ramsay et al. Blood 2012). Checkpoint blockade has been a successful therapy of many cancers including melanoma, and more recently, Hodgkin's lymphoma. Understanding expression patterns of checkpoint receptors and ligands may help in the clinical development of checkpoint blockade as a therapy for patients with CLL.Methods: Between September 2015 and April 2016, we performed 17-color multi-parameter flow-cytometry (MFC) in paired peripheral blood (PB) and bone marrow (BM) samples from 30 patients with CLL who presented as new patients for evaluation at MDACC. Patients may have received prior CLL therapy. We evaluated expression of immune receptors (inhibitory receptors: PD1, CTLA4, LAG3, TIM3; activating receptors: GITR, OX40, 41BB, ICOS) on T cell subsets: CD4 T effector cells [Teff]: CD3+CD4+CD127lo/+Foxp3-, CD4 T regulatory cells [Treg]: CD3+CD4+CD127-Foxp3+, and CD8 T cells. CLL cells were assessed for both immune receptors (as above), and ligands (4-1BBL, B7-1, B7-2, ICOSL, PDL-1, PDL-2, OX40L). These analyses were performed on freshly collected PB and BM samples by the M. D. Anderson Cancer Center Immunotherapy Platform.Results: A total of 30 patients with CLL were enrolled. The median age was 66 years (range, 35-83). Nine were women. Nineteen were treatment-naive. Prognostic markers included FISH [del(17p) = 6; del(13q) = 9, del(11q) = 4, trisomy 12 = 3, negative = 8]. IGHV mutation status was available for 19 patients (13 unmutated IGHV, 6 mutated IGHV). B2M was ≥3.5 in 11 pts.Baseline expression of costimulatory receptors in CD8 T cells in the marrow, and of the ligands in CLL cells in the marrow is shown in Figure 1. In paired PB and BM sample analysis, there was a high correlation between expression level of PD1 on Treg (Pearson correlation, r = 0.90, p<0.00001), Teff (r = 0.87, p<0.00001), CD8+ cells (r = 0.80, p<0.00001), and CLL cells (r = 0.75, p<0.00001). PD-L1 expression on CLL cells was moderately correlated between PB and BM (r = 0.57, p<0.001).Patients with prior therapy had significantly higher expression of PDL1 on the CLL cells in both PB and BM (p=0.01 and p=0.002, respectively) compared to previously untreated patients. OX40 expression on CD8 cells was significantly higher in both PB and BM in previously treated patients (compared to previously untreated patients). Patients with unmutated IGHV (p = 0.003) and del17p (p = .03) had higher PDL1 expression on CLL cells in the marrow.Conclusions: There is a strong correlation in the expression levels of PD1 on various T cell subsets between PB and BM. Clinically targetable checkpoint receptors including PD1, OX40, CTLA4, and ICOS are consistently expressed across patients with CLL, and present on cells in both PB and BM. [Display omitted] DisclosuresJain:BMS: Research Funding; Abbvie: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Infinity: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Seattle Genetics: Research Funding; Celgene: Research Funding. Burger:Roche: Other: Travel, Accommodations, Expenses; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Portola: Consultancy; Gilead: Research Funding. Thompson:Pharmacyclics: Consultancy, Honoraria. Daver:Otsuka: Consultancy, Honoraria; Ariad: Research Funding; Karyopharm: Honoraria, Research Funding; BMS: Research Funding; Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Kiromic: Research Funding. Wierda:Acerta: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Novartis: Research Funding; Abbvie: Research Funding.

A17 - Correlation of metabolic information on 18F-FDG PET with the tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) candidate to upfront surgery

A17 - Correlation of metabolic information on 18F-FDG PET with the tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) candidate to upfront surgery

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2months. Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41% (range: 0.84-14.01%), CD8-TILs of 2.9% (range: 0.11-11.92%), PD-1 of 0.65% (range: 0.02-5.87%), and PD-L1 of 0.7% (range: 0.03-10.29%). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively). The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors.

Survival Outcomes According to Adjuvant Treatment and Prognostic Factors Including Host Immune Markers in Patients with Curatively Resected Ampulla of Vater Cancer.

BackgroundAmpulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca.Methods and FindingsWe reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9–129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11–2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00–2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13–2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20–5.53) and elevated CA 19–9 (HR 1.794, 95% CI: 1.07–3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%).ConclusionsVascular invasion and elevated CA 19–9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors.

Impact of prebiotic supplementation on T-cell subsets and their related cytokines, anthropometric features and blood pressure in patients with type 2 diabetes mellitus: A randomized placebo-controlled Trial

Backgrounds and aimsType 2 diabetic mellitus (T2DM) asone of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of oligofructose-enriched inulin on T-cell subsets and their related cytokines, anthropometric and metabolic parameters in patients with T2DM. MethodsForty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of oligofructose-enriched inulin and subjects in control group received a placebo for two months. Anthropometric variables, metabolic parameters including fasting serum glucose (FSG), hemoglobin A1c (HbA1c), lipid profile and blood pressure were measured at the beginning and after two months. Immune markers also included serum interleukin (IL)-4, IL-12 and interferon (IFN)-γ concentrations were assessed and CD3+, CD4+, CD8+ and CD11b+T-cell counts were determined by flow cytometry at baseline and end of the trial. ResultsAfter two months intervention, significant improvements in anthropometric variables, blood pressure and serum lipids occurred in prebiotic-treated group (P<0.001). Serum IL-4, IL-12 and IFN-γ concentrationsalso significantly decreased in intervention group (P<0.001). No significant changes in CD3+, CD4+, CD8+ and CD11b+ T-cell counts were observed in treatment groups after intervention. ConclusionThe present study showed several beneficial effects of oligofructose-enriched inulin on the improvement of the glycemic status, lipid profile, and immune markers in patients with T2DM. Further studies are needed to confirming our findings and to better clarify the underlying mechanisms.

Autoimmune features are associated with chronic antibiotic-refractory pouchitis.

Chronic antibiotic-refractory pouchitis (CARP) occurs more frequently in patients with ileal pouch-anal anastomosis (IPAA) with concomitant autoimmune disorders. The aim of this study was to assess the overlap between dysregulated immune features in patients with IPAA and their association with CARP. We identified 150 symptomatic patients with IPAA who met inclusion criteria, including measurement of select autoimmune serology. Demographic and clinical variables were compared between patients with and without CARP. Autoimmune thyroid disease was more frequent among patients with CARP. The frequency of primary sclerosing cholangitis (16.7% versus 5.3%; P = 0.04) and serum positivity for microsomal antibody (25% versus 6.1%, P = 0.003) were significantly greater in patients with CARP compared with non-CARP patients, respectively. Increased tissue infiltration by IgG4-expressing plasma cells was detected in 17 of 31 patients (54.8%) in the CARP group as compared with 10/67 (14.9%) in the non-CARP group (P = 0.0001). Forty-seven percent of patients in the CARP group versus 22.8% in the non-CARP group had at least 2 immune features (P = 0.019). Among patients with IgG4 histology, 87% of patients in the CARP group versus 60% in the non-CARP group had at least 1 immune marker (P = 0.004). On multivariate analysis, microsomal antibody expression (odds ratio, 6.8; 95% confidence interval, 1.3-42.6; P = 0.02) and increased IgG4-expressing plasma cells tissue infiltration (odds ratio, 9.6; 95% confidence interval, 3.2-32.6, P = 0.0001) were risk factors for CARP. There is marked overlap of certain immune markers in patients with pouch dysfunction, especially those with CARP. Microsomal antibody expression and elevated IgG4-positive plasma cell infiltration were independent risk factors for CARP.

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

PurposeTo evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.Patients and methodsPatients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m2 intravenously on day 1, ifosfamide 3.5 mg/m2 intravenously on day 1, and etoposide 200 mg/m2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.ResultsDifferences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B (P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05).ConclusionAmong cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.