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Ischemic stroke is the leading cause of long-term disability in adults, accounting for 80% of stroke cases. Diffusion weighted imaging (DWI) examination is the main test for acute ischemic stroke, but in recent years, several studies have shown that some patients show negative DWI examination after the onset of ischemic stroke with symptoms of significant neurological deficits. In this study, we investigated potential biomarkers related to immune metabolism in the peripheral blood of DWI-negative versus DWI-positive patients after ischemic stroke and explored their possible regulatory processes in ischemic stroke. The datasets related to ischemic stroke were downloaded from the GEO database, immune-related genes and metabolism-related genes were obtained from the ImmPort database and MSigDB database, respectively, and immune-related differential genes were obtained based on immune scores using the algorithm of the R software package "GSVA." Candidate genes were selected based on intersections, hub genes were screened using the algorithm in Cytoscape software, and finally, GeneMANIA analysis, GSEA enrichment analysis, subcellular localization, gene transcription factor and gene-drug interaction networks, and disease correlation analyses were performed for the hub genes. Five hub genes (GART, TYMS, PPAT, CTPS1, and PAICS) were obtained by PPI network analysis and software analysis. Among them, PPAT and PAICS may be the real hub genes with consistent and significantly differentiated results from the discovery and validation sets. The functions of these hub genes may be related to pathways such as nucleotide biosynthetic processes. The constructed hub gene ceRNA network showed that hsa-10a-5p is the key miRNA connecting PAICS and multiple lncRNAs in this study. Differential genes related to immunity and metabolism in DWI-negative and DWI-positive patients after IS were identified using bioinformatics analysis, and their pathways and related TF-RNAs, miRNAs, and lncRNAs were identified. These genes may be considered effective targets for the diagnosis and treatment of ischemic stroke., (© 2024. The Author(s).)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmune disorder characterized by numerous symptoms of unknown etiology. The ME/CFS immune markers reported so far have failed to generate a clinical consensus, perhaps partly due to the limitations of biospecimen biobanking. To address this issue, we performed a comparative analysis of the impact of long-term biobanking on previously identified immune markers and also explored additional potential immune markers linked to infection in ME/CFS. A correlation analysis of marker cryostability across immune cell subsets based on flow cytometry immunophenotyping of fresh blood and frozen PBMC samples collected from individuals with ME/CFS (n = 18) and matched healthy controls (n = 18) was performed. The functionality of biobanked samples was assessed on the basis of cytokine production assay after stimulation of frozen PBMCs. T cell markers defining Treg subsets and the expression of surface glycoprotein CD56 in T cells and the frequency of the effector CD8 T cells, together with CD57 expression in NK cells, appeared unaltered by biobanking. By contrast, NK cell markers CD25 and CD69 were notably increased, and NKp46 expression markedly reduced, by long-term cryopreservation and thawing. Further exploration of Treg and NK cell subsets failed to identify significant differences between ME/CFS patients and healthy controls in terms of biobanked PBMCs. Our findings show that some of the previously identified immune markers in T and NK cell subsets become unstable after cell biobanking, thus limiting their use in further immunophenotyping studies for ME/CFS. These data are potentially relevant for future multisite intervention studies and cooperative projects for biomarker discovery using ME/CFS biobanked samples. Further studies are needed to develop novel tools for the assessment of biomarker stability in cryopreserved immune cells from people with ME/CFS., Competing Interests: JR is an employee at the Rigau Private Clinic. JB is the founder and CEO and JC is also co-founder and CSO (AlbaJuna Therapeutics, Barcelona, Spain). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gómez-Mora, Carrillo, Urrea, Rigau, Alegre, Cabrera, Oltra, Castro-Marrero and Blanco.)

Objectives: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression., Methods: LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann-Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables., Results: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs., Conclusions: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression., (© 2019 British HIV Association.)

Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance. This review focuses on the necessity for such immune status biomarkers, which could predict complications prior to their appearance. Herein we bring examples for the use of cellular and molecular biomarkers in diagnosis, prognosis and follow-up of patients suffering from various cancers, for prediction of response to immune-based anti-cancer therapy and for prediction of cardiovascular disease in type 2 diabetes patients. Monitoring such biomarkers is expected to have a major clinical impact in addition to unraveling of the entangled complexity underlying dysregulated immunity in chronic inflammation. Thus, newly discovered biomarkers and those that are under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.

Introduction: Expression of immune markers is of scientific interest because of their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune markers, there are few data regarding this context., Methods: A 76-year-old never-smoking female with EGFR-mutated lung adenocarcinoma (AC) acquired resistance to gefitinib. After her death, an autopsy revealed SCLC transformation and EGFR T790M secondary mutation (T790M) as mutually exclusive resistance mechanisms occurring differently in different metastases; two liver metastases (SCLC versus AC with T790M) and two lymph node metastases (SCLC versus AC with T790M) were analyzed to compare the expression status of immune markers by immunohistochemistry and by an immune oncology gene expression panel., Results: Programmed death ligand 1 (PD-L1) protein was partially expressed in tumor cells with AC lesions (T790M) but not in tumor cells with SCLC transformation. The liver metastasis with SCLC transformation showed no stromal PD-L1 expression and scant tumor-infiltrating lymphocytes, whereas the other lesions demonstrated stromal PD-L1 staining and infiltration of CD8-positive T cells. Data generated using an immuno-oncology gene expression panel indicated a higher level of T-cell costimulatory molecules and lower expression of type I interferon-regulated genes in lesions with SCLC transformation., Conclusion: These data highlight the heterogeneity of expression of immune markers depending on the metastatic sites and histological transformation and indicate that the biopsy specimen from one lesion may not be representative of immune marker status for all lesions., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Male and female rats (26-day old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Sperm positive females remained within their dose groups and were exposed to AgAc during gestation and lactation. Splenic and thymic lymphocyte subsets from F1 generation PD (postnatal day) 4 and 26 pups were assessed by flow cytometry for changes in phenotypic markers. Spleens from PD4 pups had lower percentages of CD8 + lymphocytes in 4 and 40 mg/kg AgAc exposed groups and reduced Concanavalin A (Con A) response at all AgAc exposure groups. Splenic maturation increased in PD26 pups compared to PD4 pups. Con A and lipopolysaccharide (LPS) mediated splenic responses were lower in PD26 pups exposed to 40 mg/kg AgAc. Changes in PD 26 pup splenocyte phenotypic markers included lower TCR + cells at 4 and 40 mg/kg AgAc exposure and higher B cell population in the 40 mg/kg AgAc. PD26 pup splenic natural killer cell (NK) activity was higher in the 0.4 AgAc group and unchanged in 4 and 40 mg/kg AgAc groups. In conclusion, maternal exposure to AgAc had a significant impact on rat splenic development during the early lactation period., (Published by Elsevier Ltd.)

Simple Summary: The armamentarium of first-line systemic therapy for patients with unresectable non-small cell lung cancer (NSCLC) has been rapidly expanding over the past two decades. Currently, about 50% of patients with NSCLC do not need chemotherapy as first-line treatment. For these patients, molecularly targeted therapy and immune checkpoint inhibitor therapy have significantly improved progression-free survival and overall survival with favorable toxicity profiles. Patient demographics and clinical features are not sufficient for the selection of these treatments. An unmet need of precision oncology is to select the most appropriate therapeutic regimen with maximal efficacy and minimal unwanted toxicity for individual patients with NSCLC based on the assessment of their molecular and immune biomarkers at diagnosis. In this review, we summarize the current data and propose a practical algorithm for implementing precision biomarker testing at diagnosis and selecting the most appropriate first-line systemic therapy for patients with unresectable, advanced, or metastatic NSCLC. First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number of gain-of-function molecular targets has been shown to improve progression-free survival (PFS) and overall survival (OS) with favorable toxicity profiles compared to platinum-containing chemotherapy and can be given as first-line systemic therapy in ~25% of patients with NSCLC. Actionable genetic alterations include EGFR, BRAF V600E, and MET exon 14 splicing site-sensitizing mutations, as well as ALK-, ROS1-, RET-, and NTRK-gene fusions. Secondly, inhibitors of programmed cell death protein 1 or its ligand 1 (PD-1/L1) such as pembrolizumab, atezolizumab, or cemiplimab monotherapy have become a standard of care for ~25% of patients with NSCLC whose tumors have high PD-L1 expression (total proportion score (TPS) ≥50%) and no sensitizing EGFR/ALK alterations. Lastly, for the remaining ~50% of patients who are fit and whose tumors have no or low PD-L1 expression (TPS of 0–49%) and no sensitizing EGFR/ALK aberrations, platinum-containing chemotherapy with the addition of a PD-1/L1 inhibitor alone or in combination of a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor improves PFS and OS compared to chemotherapy alone. The objectives of this review are to summarize the current data and perspectives on first-line systemic treatment in patients with unresectable NSCLC and propose a practical algorithm for implementing precision biomarker testing at diagnosis. [ABSTRACT FROM AUTHOR]

First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number of gain-of-function molecular targets has been shown to improve progression-free survival (PFS) and overall survival (OS) with favorable toxicity profiles compared to platinum-containing chemotherapy and can be given as first-line systemic therapy in ~25% of patients with NSCLC. Actionable genetic alterations include EGFR, BRAF V600E, and MET exon 14 splicing site-sensitizing mutations, as well as ALK-, ROS1-, RET-, and NTRK-gene fusions. Secondly, inhibitors of programmed cell death protein 1 or its ligand 1 (PD-1/L1) such as pembrolizumab, atezolizumab, or cemiplimab monotherapy have become a standard of care for ~25% of patients with NSCLC whose tumors have high PD-L1 expression (total proportion score (TPS) ≥50%) and no sensitizing EGFR/ALK alterations. Lastly, for the remaining ~50% of patients who are fit and whose tumors have no or low PD-L1 expression (TPS of 0–49%) and no sensitizing EGFR/ALK aberrations, platinum-containing chemotherapy with the addition of a PD-1/L1 inhibitor alone or in combination of a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor improves PFS and OS compared to chemotherapy alone. The objectives of this review are to summarize the current data and perspectives on first-line systemic treatment in patients with unresectable NSCLC and propose a practical algorithm for implementing precision biomarker testing at diagnosis.

Simple Summary: Future reproduction methods for boosting crucial traits will likely be influenced by the proportion of genetic and phenotypic variances. Using PCR-DNA sequencing, the variations in the nucleotide sequences of the immunological genes between healthy buffaloes and buffaloes suffering from inflammatory reproductive disorders were discovered. When buffaloes experienced inflammatory reproductive disorders, they were more likely to express the examined genes. The molecular alterations may, therefore, provide crucial information about the relationships between the physiologies of the various reproductive pathways and help diagnose inflammatory postpartum disorders. The immunological genes that may interact with inflammatory postpartum diseases in Italian buffaloes were examined in this study. A total number of 120 female Italian buffaloes (60 normal and 60 with inflammatory reproductive diseases) were employed. Each buffalo's jugular vein was pierced to get five milliliters of blood. To obtain whole blood and extract DNA and RNA, the blood was placed within tubes containing sodium fluoride or EDTA anticoagulants. The immunological (IKBKG, LGALS, IL1B, CCL2, RANTES, MASP2, HMGB1, and S-LZ) genes' nucleotide sequence differences between healthy buffaloes and buffaloes affected by inflammatory reproductive diseases were found by employing PCR-DNA sequencing. According to Fisher's exact test (p ˂ 0.01), there were noticeably different probabilities of all major nucleotide changes spreading among buffalo groups with and without reproductive problems. Buffaloes were significantly more likely to express the examined genes when they had inflammatory reproductive diseases. The outcomes might support the significance of these markers' nucleotide variations and gene expression patterns as indicators of the prevalence of inflammatory reproductive disorders and provide a workable buffalo management policy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pneumonia is a commonly encountered problem in small ruminant medicine practice that negatively affects goat breeding. Some of the limitations of the conventional approaches used by animal breeders to promote animal health may be overcome with the use of molecular genetic tools. Using PCR-DNA sequencing in pneumonia-affected and -resistant Baladi goats, SNPs associated with pneumonia resistance/susceptibility were found in the SLC11A1, CD-14, CCL2, TLR1, TLR7, TLR8, TLR9, β defensin, SP110, SPP1, BP1, A2M, ADORA3, CARD15, IRF3, and SCART1 genes. These indicators' mRNA levels were different in both the healthy and affected goats. Therefore, to improve the effectiveness of animal selection for innate resistance, finding potential genes linked to pneumonia risk may be crucial. The effectiveness of breeding for inherent disease resistance in animals could be considerably increased by identifying the genes and mutations that cause diversity in disease resistance. One hundred and twenty adult female Baladi goats (sixty pneumonic and sixty apparently healthy) were used in this study. DNA and RNA were extracted from blood samples collected from the jugular vein of each goat. SLC11A1, CD-14, CCL2, TLR1, TLR7, TLR8, TLR9, β defensin, SP110, SPP1, BP1, A2M, ADORA3, CARD15, IRF3, and SCART1 SNPs that have been previously found to be associated with pneumonia resistance/susceptibility were identified via PCR-DNA sequencing. The pneumonic and healthy goats differed significantly, according to a Chi-square analysis of the discovered SNPs. The mRNA levels of the studied immune markers were noticeably greater in the pneumonic goats than in the healthy ones. The findings could support the significance of the use of immune gene expression profiles and nucleotide variations as biomarkers for the susceptibility/resistance to pneumonia and provide a practical management technique for Baladi goats. These results also suggest a potential strategy for lowering pneumonia in goats by employing genetic markers linked to an animal's ability to fend off infection in selective breeding. [ABSTRACT FROM AUTHOR]

Background: Ras guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the correlation between RASGRP2 and immune infiltration and malignant features in lung adenocarcinoma (LUAD) has rarely been mentioned. Methods: The Limma package and the LASSO regression model were performed to screen for differentially expressed genes. Data from the TCGA and 5 GEO databases were used to explore the expression level of RASGRP2 in LUAD patients. A weighted co-expression network and LinkFinder module were established to find the related genes of RASGRP2. The ESTIMATE algorithm was used to analyze the correlation between RASGRP2 and immune infiltration in LUAD. Tumorinfiltrating immune cells were sorted and sequenced at the single-cell level to analyze differences in RASGRP2. Real-time PCR and immunohistochemistry were performed in the real-world cohort to verify the expression of RASGRP2 and its correlation with immune-related genes. Clone formation and EdU assays were used to verify the proliferation ability. The proportion of apoptotic cells was analyzed by flow cytometry. Observation of mitochondrial membrane potential (MMP) changes by fluorescence microscopy. Results: Our results suggested that decreased RASGRP2 was associated with worse clinical parameters and prognosis in LUAD patients. And we constructed a FLI1-HSA-miR-1976-RASGRP2 transcriptional network to support the role of RASGRP2. Enrichment analysis revealed that RASGRP2 was involved in lymphocyte activation and leukocyte adhesion. RASGRP2 was found to be positively correlated with the infiltration of most immune cel l s, immunoregulators, and chemokines in a subsequent study. Meanwhile, the realworld cohort confirmed that the expression levels of PDCD1, CTLA4, CD40LG, CCL14, CXCR5, and CCR7 were higher in the high-RASGRP2 expression group. Cytological experiments proved that RASGRP2 inhibited cell proliferation in LUAD by regulating mitochondrial-dependent apoptosis. Conclusion: RASGRP2 was a potential immune-related biomarker of LUAD. In addition, RASGRP2 was involved in the malignant progression of LUAD through the regulation of mitochondrial-dependent apoptosis. [ABSTRACT FROM AUTHOR]

COVID‐19 is a world disaster. In response to COVID‐19 quarantine, stress, anxiety, and depression may easily develop which negatively affect immunity and decrease the patient's response against the COVID‐19 virus. This study investigated the effect of an integrated intervention combining cognitive‐behavioural stress management (CBSM) and progressive muscle relaxation (PMRs) on immune biomarkers and disease severity and progression in patients with COVID‐19 and the period to which these changes last. Thirty patients with mild or moderate COVID‐19 were randomly distributed into intervention and control groups. The intervention group performed an integrated intervention combining CBSM and PMRs. There were three outcome measures including blood immune markers, salivary immunoglobulin A, and Wisconsin scale (WIS). Two‐week post‐intervention, there were significant differences between groups in the WIS total score, Leucocytes, Lymphocytes, Interleukin‐6, and Immunoglobulin‐A. While there were non‐significant differences between both groups in Interleukin‐10 and TNF‐α. The significant differences between groups in the WIS total score, Leucocytes, Lymphocytes, Interleukin‐6, and Immunoglobulin‐A significantly continued 1 week as a follow‐up. This study concluded that performing an integrated intervention combining CBSM and PMRs for 2 weeks significantly increases immune biomarkers mainly Leucocytes, Lymphocytes, Interleukin‐10, and Interleukin‐6 along with S‐IgA. Also, this protocol significantly decreases disease severity and associated stress, anxiety, and depression; and enhances the quality of life in patients with COVID‐19. The study was retrospectively registered with NCT04998708. [ABSTRACT FROM AUTHOR]

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a serious complication in clinical settings. This study aimed to elucidate the immune molecular mechanisms underlying ALI by bioinformatics analysis. Human ALI and six ALI mouse model datasets were collected. Immune cell infiltration between the ALI samples and non-ALI controls was estimated using the ssGSEA algorithm. Least absolute shrinkage and selection operator (LASSO) regression analysis and Wilcoxon test were performed to obtain the significantly different immune cell infiltration types. Immune feature genes were screened by differential analysis and the weighted correlation network analysis (WGCNA) algorithm. Functional enrichment was then performed and candidate hub biomarkers were identified. Finally, the receiver operator characteristic curve (ROC) analysis was used to predict their diagnostic performances. Three significantly different immune cell types (B cells, CD4 T cells, and CD8 T cells) were identified between the ALI samples and controls. A total of 13 immune feature genes were obtained by WGCNA and differential analysis and found to be significantly associated with immune functions and lung diseases. Four hub genes, including CD180, CD4, CD74, and MCL1 were identified using cytoHubba and were shown to have good specificity and sensitivity for the diagnosis of ALI. Correlation analysis suggested that CD4 was positively associated with T cells, whereas MCL1 was negatively correlated with B and T cells. We found that CD180, CD4, CD74, and MCL1 can serve as specific immune biomarkers for ALI. MCL1–B cell, MCL1–T cell, and CD4–T cell axes may be involved in the progression of ALI. [ABSTRACT FROM AUTHOR]

Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMB H. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMB H. The incidence of 'triple positive" cases was less than 2%. • This study analyzes PD-L1, MSI, and TMB in 16,300 gynecologic cancer specimens. • Gynecologic cancers have markedly variable response to immunotherapy. • Gynecologic cancers with one immune biomarker are more likely to be positive for others. [ABSTRACT FROM AUTHOR]

For several years, the role of immune system in the pathophysiology of psychosis has been well-recognized, showing differences from the onset to chronic phases. Our study aims to implement a biomarker-based classification model suitable for the clinical management of psychotic patients. A machine learning algorithm was used to classify a cohort of 362 subjects, including 160 first-episode psychosis patients (FEP), 70 patients affected by chronic psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder) with psychosis (CRO) and 132 health controls (HC), based on mRNA transcript levels of 56 immune genes. Models distinguished between FEP, CRO, and HC and between the subgroup of drug-free FEP and HC with a mean accuracy of 80.8% and 90.4%, respectively. Interestingly, by using the feature importance method, we identified some immune gene transcripts that contribute most to the classification accuracy, possibly giving new insights on the immunopathogenesis of psychosis. Therefore, our results suggest that our classification model has a high translational potential, which may pave the way for a personalized management of psychosis. [ABSTRACT FROM AUTHOR]

The current study was aimed to evaluate therapeutic efficacy of human umbilical cord-mesenchymal stem cells (HUC-MSCs) to repair of radial nerve injury through estimation of clinical status, serum biomarkers and hematology. A total 18 stray, male dogs of 12-18 months of age and 8-10Kg of weight were selected, examined clinically, subjected to a preparation period, and divided into 3 equal groups; 1stG (experimental group) in which radial nerve of study animals was cut surgically and treated with HUC-MSCs; 2ndG (positive control group) in which, radial nerve of study animals was cut, but not treated with HUC-MSCs, and the 3rdG (negative Control group) in which radial nerve neither cut nor treated with HUC-MSCs. During 16 weeks, all study dogs were feed and let drink from the same source and received a high management care. In 1stG, significant motive dysfunction with apparent decline in appetite, changes in sleeping habits, slight increase in temperature, shallow and rapid breathing, and slight tachycardia were showed in 1st week. During 2nd to 5th weeks, there was apparent improvement in general and physical activity with the ability of 1stG animals to extend their forelimb and standup normally, but with lameness. At 16th week, clinical status was normal with absence of forelimb muscle atrophy, lameness, and motive dysfunction. Concerning to immune-biomarkers, significant increases (P<0.05) were reported in levels of IgG and TNF-á and significant reduction (P<0.05) in IL-10 were detected at 4th and 6th, 2nd and 4th and 2nd, 4th and 6th weeks respectively. Regarding to hematology, there were significant increases in total WBCs, lymphocytes and monocytes but not in neutrophils (P>0.05) were reported at 4th and 6th weeks of study. In conclusion, positive outcomes achieved in this study suggesting effective role of HUC-MSCs in repairing of radial NI and offered a great promise for some disease treatment. [ABSTRACT FROM AUTHOR]

Background: Monocyte‐to‐lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor‐related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). Material and Methods: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009–2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR‐LDH combined (group 1: MLR‐LDH low; group 2: MLR or LDH high; group 3: MLR‐LDH high). The second cohort was used to validate the model. Results: At the median follow‐up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39–4.04), high LDH (HR, 1.73; 95% C.I., 1.03–2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62–4.66), and group 3 (HR, 3.73; 95% C.I., 1.94–7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. Conclusion: MLR and LDH are circulating cost‐effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. Implications for Practice: High monocyte‐to‐lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR‐LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR‐LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC. Evidence suggests a pivotal role of the crosstalk between tumor microenvironment and the immune system that may be a hallmark of spreading cancer. This article evaluates the prognostic role of monocyte‐to‐lymphocyte ratio and levels of lactate dehydrogenase in patients with metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Neoadjuvant (preoperative) approach to breast cancer treatment has become widely accepted. Traditionally, the primary objective of neoadjuvant treatment is to improve subsequent surgical intervention and the effectiveness is often evaluated by its ability to achieve complete pathological response (pCR) and the eradication of the malignant disease in the breast and axillary lymph nodes. More recently, neoadjuvant treatment has also become recognized as an in vivo, preoperative" window of opportunity" to explore the efficacy of novel agents such as immunotherapies where several tumor biomarkers are also routinely collected to quantify antitumor immunity. However, one challenge to combine the traditional pCR and efficacy biomarkers is that these tumor biomarkers are only partially available and cannot be measured in patients who have achieved pCR. In this article, a stepwise hypothesis testing procedure is proposed to combine a continuous tumor biomarker with the conventional binary endpoint in a two-arm randomized phase II superiority trial to improve statistical power. The operating characteristics of the proposed procedure are illustrated with a real-world example and the performance is also evaluated numerically. [ABSTRACT FROM AUTHOR]

Currently, breast cancer accounts for a quarter of all cancers and 15% of cancer-specific deaths amongst females. The global occurrence of breast cancer has increased in the last decade whilst the mortality rate has decreased. Exercise can be beneficial to breast cancer patients through changes in adiposity and immune responses. Even though there is some evidence supporting the improvement of fat metabolism and immune function after an exercise program in breast cancer, randomized controlled studies are limited and require further comprehensive analysis in this population group. Herein, we identify the known effects of exercise programs on adiposity and immunological markers which can improve breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose <1 Gy). At higher doses, ionizing radiation, especially in combination with additional immune stimulation, fosters the induction of immunogenic forms of tumor cell death and shifts the tumor microenvironment as well as the infiltration of immune cells from an anti- to a pro-inflammatory state. Distinct tumor infiltrating immune cells predict the response to radiochemotherapy in a multitude of tumor entities. While a high tumor infiltration of these adaptive immune cells mostly predicts a favorable disease outcome, a high infiltration of tumor-associated macrophages predicts an unfavorable response. Pro-inflammatory events should dominate over anti-inflammatory ones in this scenario. This review focuses on how ionizing radiation modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the relationship between the level and function of circulating immune cells with average daily gain, live and carcass measurements, feed intake, and feed conversion. Production performance was monitored throughout the pig's lifetime. Pigs were moved in weekly batches through the nursery and growing/finishing rooms at specific target weights. Animals were individually weighed at birth and at weaning, and then every two weeks while they were “on test” until they were “off test” and sent to the slaughterhouse. At six to seven weeks of age, the pigs were bled in the nursery. The percentage of immune cell subsets and lymphocyte proliferation was estimated using swine monoclonal antibodies and flow cytometric analysis. The predictive effect of the immune cell subset markers and lymphocyte proliferation on production traits was statistically analyzed. The results indicated that the proportion of several peripheral cell subsets, including CD16+, CD2+/CD16+, and CD8+ lymphocytes, appear to predict growth during the entire productive life of the pig. Larger percentages of lymphocytes expressing CD16+ CD2+/CD16+, and CD8+receptors in blood resulted in a reduction in average daily gain. In addition, high percentages of SLA-DQ+ cells were associated with better carcass weight and feed conversion. The CD16+, CD2+/CD16+, CD8+, and SLA-DQ± cell subsets appear to be important biomarkers involved with the inherent ability of the pig to efficiently grow and produce better carcass weight in representative commercial environments. [ABSTRACT FROM AUTHOR]

The authors examined the relationship between immune biomarkers and indoor air pollution cross-sectionally in school children 9-11 yr of age who had immunologically related respiratory diseases and who resided in Hungarian cities. Nitrogen dioxide, formaldehyde, benzene, xylene, and toluene were measured passively indoors prior to the collection of venous blood samples for blood counts and identification of immune biomarkers. House dust mite allergen was also measured. Numerous immune biomarkers were significantly elevated in these sensitive children, compared with normal children, and several biomarker alterations in these children were related to high concentrations of air pollutants in the home. The strongest and most significant associations were seen between high indoor nitrogen dioxide concentrations and increased white blood cells, monocytes, red blood cells, and immunoglobulin G (IgG), as well as decreased immunoglobulin M (IgM) and Klebsiella pneumoniae-specific IgM. Bacterial-specific IgGs were related significantly to formaldehyde concentrations. These findings suggest the important role of indoor air pollutants in immune reactions. [ABSTRACT FROM AUTHOR]

Evidence from animal studies suggests that DDT and DDE can adversely affect immuno-competence while human data are less conclusive. We aimed to assess the association of plasma concentrations of DDT and DDE with biomarkers of inflammation among reproductive-aged women residing in homes sprayed with DDT through Indoor Residual Spraying (IRS). This study included 416 women from the Study of Women and Babies, South Africa (2010–2011). DDT, DDE, and biomarkers of inflammation (immunoglobulins A, G and M, interleukins 1β, 6, and 8, tumor necrosis factor-α, C-reactive protein, serum amyloid-A, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) were quantified in plasma. Linear regression was used to assess associations of DDT and DDE with each natural log-transformed biomarker. Models were adjusted for age, body mass index, parity, income, and season; beta estimates were expressed as percent differences. Compared to women with the lowest plasma concentrations of DDT and DDE, those with the highest concentrations of both compounds had higher levels IL-1β, IL6, and TNF- α. While associations were statistically significant for both DDT and DDE, the magnitude of the associations was slightly stronger for DDT. Compared to women in the lowest quintile of DDT, women in the highest quintile were estimated to have 53.0% (95%CI: 21.7%, 84.4%), 28.1% (95%CI: 6.4%, 49.8%), and 26.6% (95%CI: 12.0%, 41.1%) higher levels of IL-1β, IL6, and TNF- α, respectively. Our results suggest that increased plasma concentrations of DDT and DDE resulting from exposure to IRS may increase concentrations of pro-inflammatory biomarkers among reproductive-aged women in South Africa. • Assessed the effect of DDT exposure (via IRS) on immune markers among reproductive-aged women. • Plasma DDE and DDT were positively associated with pro-inflammatory biomarkers. • Associations with plasma DDE and DDT were not consistent across all immune markers assessed. • Study participants had higher concentrations IgG than US black females. [ABSTRACT FROM AUTHOR]

It is estimated that pancreatic cancer will be the second leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options for this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are not completely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, relatively poorer antigenicity compared to other solid tumors, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological, would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored. [ABSTRACT FROM AUTHOR]

Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy. [ABSTRACT FROM AUTHOR]

Existing clinical, anatomopathological and molecular biomarkers fail to reliably predict the prognosis of cutaneous melanoma. Biomarkers for determining which patients receive adjuvant therapies are needed. The emergence of new technologies and the discovery of new immune populations with different prognostic values allow the immune network in the tumor to be better understood. Importantly, new molecules identified and expressed by immune cells have been shown to reduce the antitumor immune efficacy of therapies, prompting researchers to develop antibodies targeting these so-called “immune checkpoints”, which have now entered the oncotherapeutic armamentarium. [ABSTRACT FROM AUTHOR]