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Monocyte-platelet interaction may favor the development of a proatherogenic monocyte phenotype. It is still uncertain which of the 3 monocyte subpopulations interact with platelets to form monocyte-platelet aggregates (MPAs) in acute myocardial infarctions. The aim of our study was to evaluate the monocyte subsets, the percentage of MPAs and the involvement of monocyte subsets in MPA formation among patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), and compared to patients with stable angina (SA).

The traditional health care model is focused on diseases (medicine and natural science) and does not acknowledge patients’ resources and abilities to be experts in their own life based on their lived experiences. Improving health care safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people’s values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) from guidelines to digital care pathways, (5) embedding Planetary Health, (6) novel classification of rhinitis and asthma, (7) embedding real-life data with population-based studies, (8) the ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) artificial intelligence, (10) the development of digitally enabled, ARIA person-centered care, and (11) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.

•Concentrations of miR-155 and miR-146 increase simultaneously in AMI patients.•miR-155/miR-146 balance regulates monocyte recruitment.•Blood monocytes activation reflects macrophages accumulation in the infarct zone.•In AMI frequencies of CD16+ monocytes increase whereas classical cells decreases.•IL-6 reflects the range of necrosis, IL-10 may protect left ventricle function.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk. This is also endorsed by many major medical societies and advocacy group stakeholders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.

Advances in molecular analyses based on high-throughput technologies can contribute to a more accurate classification of non–small cell lung cancer (NSCLC), as well as a better prediction of both the disease course and the efficacy of targeted therapies. Here we set out to analyze whether global gene expression profiling performed in a group of early-stage NSCLC patients can contribute to classifying tumor subtypes and predicting the disease prognosis. Gene expression profiling was performed with the use of the microarray technology in a training set of 108 NSCLC samples. Subsequently, the recorded findings were validated further in an independent cohort of 44 samples. We demonstrated that the specific gene patterns differed significantly between lung adenocarcinoma (AC) and squamous cell lung carcinoma (SCC) samples. Furthermore, we developed and validated a novel 53-gene signature distinguishing SCC from AC with 93% accuracy. Evaluation of the classifier performance in the validation set showed that our predictor classified the AC patients with 100% sensitivity and 88% specificity. We revealed that gene expression patterns observed in the early stages of NSCLC may help elucidate the histological distinctions of tumors through identification of different gene-mediated biological processes involved in the pathogenesis of histologically distinct tumors. However, we showed here that the gene expression profiles did not provide additional value in predicting the progression status of the early-stage NSCLC. Nevertheless, the gene expression signature analysis enabled us to perform a reliable subclassification of NSCLC tumors, and it can therefore become a useful diagnostic tool for a more accurate selection of patients for targeted therapies.

To date, early effects of specific immune therapy on the parameters of adaptive immune responses in hymenoptera venom allergic patients remain unclear. Therefore, in this pilot study, we aimed to evaluate early changes in the levels of CD25 expression within CD4+ T cells occurring in the course of ultra-rush wasp venom immunotherapy. To this end, ten wasp venom-sensitive patients subjected to ultra-rush immune therapy were recruited for the study. CD4+ T cells and CD25 expression were assessed before the start of treatment, 24h later and on day 120 with the use of monoclonal antibodies directed at CD4, CD25 (IL-2 receptor) by the means of multi-color flow cytometry. We have demonstrated non-significant decrease in the intensity of CD25 expression on the surface of CD4+ T cells at day 1 but not day 120 of specific immune therapy. Our study suggests that putative early immunosuppressive mechanisms of SIT are not related to dramatic changes in the expression of CD25 on CD4+ T cells.

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types.

Allergic diseases are the most common chronic conditions lasting throughout the patient's life. They not only cause significant deterioration in the quality of life of patients but also lead to significant absenteeism and reduced productivity, resulting in very high costs for society. Effective and safe treatment of allergic diseases is therefore one of the main challenges for public health and should be carried out by all the specialists in family medicine, internists and paediatricians in collaboration with allergists, otorhinolaryngologists and dermatologists. Antihistamines are most commonly used in the treatment of allergies. Several dozen drugs are available on the pharmaceutical market, and their generic forms are advertised widely as very effective drugs for the treatment of allergic diseases. What is the truth? What are the data from clinical trials and observational studies? Are all drugs equally effective and safe for the patient? According to a panel of experts representing various fields of medicine, inappropriate treatment of allergies can be very risky for patients, and seemingly equally acting medications may differ greatly. Therefore, a panel of experts gathered the latest data from the entire scientific literature and analyzed the latest standards and recommendations prepared by scientific societies. This paper provides a summary of these studies and highlights the importance for the patient of the proper choice of drug to treat his allergies.

Recently, identification of CD25 (interleukin-2 receptor alpha) expression on leukemic blasts was correlated to early treatment failure and unfavorable outcome in acute myeloid leukemia (AML) patients. Here we wished to determine whether quantification of CD25 on peripheral blood CD4+ T cells could improve prognostication in newly diagnosed AML patients.

Glucocorticoid (GC) resistance (GR) poses a serious clinical problem affecting a proportion of asthmatic patients. Thus the efforts aimed at exploring therapeutic methods allowing for overcoming GR are still warranted. To date, vitamin D3 was found to exert certain effects indicating that it can potentially supplement the effects of GC therapy in asthmatic patients. Here we wished to investigate whether treatment with GC and/or vitamin D3 can modulate the expression of one of crucial immunomodulatory molecules accounting for suppressive actions of natural regulatory T cells (Treg cells), namely forkhead box P3 (FoxP3). We demonstrated here that 24h in vitrostimulation with either GC or vit. D3 (alone or in combination) did not significantly affect neither frequencies of CD4+FoxP3+ T cells or the levels of expression of FoxP3 within CD4+ T cells derived from healthy individuals. Therefore we hypothesize that anti-inflammatory actions of both GC and vit. D3 do not seem to be directly related to changes in the expression of FoxP3 in CD4+ T cells.

Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in adults. CLL is characterized by numerous immune disorders leading to the development of infections which have become the major cause of death in this group of patients. According to recent reports, many of immune alterations observed in the course of CLL could be attributed to dysfunctions of monocytes/macrophages and other cells of myeloid linage. In this article, we summarized the data on the role of monocytes and monocyte-derived cells in the pathogenesis of CLL.

Glucocorticoids (GC) exert some of their anti-inflammatory actions via enhancement of interleukin-10 (IL-10) production by immune cells. Interestingly, however, we previously demonstrated that oral administration of GC to asthmatic patients resulted in down-regulation of interleukin-10 receptor (IL-10R) expression on peripheral blood leukocytes. Here we wished to investigate whether addition of vitamin D3 (vit. D3) could abrogate these down-regulating actions of GC. We performed a comparative analysis of the effects of in vitro stimulation with GC and/or vit. D3 on surface expression of IL-10R on the CD4+ T cell pool. As expected, GC stimulation led to significant reduction of IL-10R. In contrast, culture in the presence of vit. D3 did not result in any significant changes of IL-10R expression. Moreover, addition of vit. D3 to GC culture did not alter GC-induced down-regulation of IL-10R expression. Thus, we conclude that anti-inflammatory actions of vit. D3 are not dependent on modification of IL-10R expression.

In this paper we review and discuss three of the most exciting and promising cytokines for therapeutic intervention and immunomodulation of immune responses including those on mucosal surfaces. The main properties of IL-12, IL-15 and IL-7 are described and the studies utilizing these cytokines as immunomodulators and vaccine adjuvants discussed.

ABSTRACTWe investigated whether the choice of anticoagulant or the application of density gradient mononuclear cell isolation may account for conflicting published data regarding the levels of the scavenger receptors' expression in healthy individuals. We demonstrate that the detection of CD163, but not CD36, differs dramatically among the methods.

Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs.

Interleukin-7 (IL-7) is important for thymopoiesis in mice and humans because IL-7 receptor α (IL-7Rα) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis. Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)–infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC+) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4- depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4+ and CD8+ T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell–replete and T-cell–depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination.

ABSTRACTMost human immunodeficiency virus (HIV) type 1 infections occur by the mucosal route. Thus, it is important to assess the immune responses to HIV in the vaginal, cervical, and rectal compartments. Here we quantitated the virus-specific CD8+T-cell response and characterized the phenotype of lymphocytes in the genital tracts of naive macaques, macaques acutely or chronically infected with simian immunodeficiency virus SIVmac251, and macaques chronically infected with chimeric simian/human immunodeficiency virus SHIVKU2.Vaginal biopsy samples or samples obtained at the time of euthanasia were used in this analysis. The percentage of Gag-specific, tetramer-positive T cells was as high as 13 to 14% of the CD3+CD8+T-cell population in the vaginal and cervical laminae propriae of both SIVmac251and SHIVKU2chronically infected macaques. In most cases, the frequency of this response in the cervicovaginal compartment far exceeded the frequency in the blood or the draining iliac lymph node. Vaginal laminae propriae of naive macaques contained 55 to 65% CD3+CD8+cells and 28 to 34% CD3+CD4+cells, while the majority of intraepithelial cells were CD8+T cells (75 to 85%). For the same cells, the surface expression of CD62L was low whereas that of aEß7 was high. No difference in the expression of CD45RA on CD8+T cells was observed in the chronic stage of SIVmac251infection. Although no decrease in the percentage of CD4+cells in the genital tract was observed within the first 12 days of infection, by 6 weeks from SIVmac251infection and thereafter the percentage of CD4+T cells was decreased in the laminae propriae of the vagina and cervix. Expression of CD45RA did not differ in naive and acutely SIVmac251infected macaques. Information on the quality and quantity of local immune responses may help in the design of vaccine strategies aimed at containing viral replication at the site of viral encounter.

ABSTRACTThe identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8+T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8+and CD4+T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIVmac251and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4+T cells. The frequency of the Gag 181 (p11C, C?M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8+T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIVmac251that were progressing to disease. Overall, the functionality of CD8+tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIVmac251-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8+T-cell function.

The aim of the experiment was to evaluate the process of neutrophil extracellular traps (NETs) formation in patients with oral squamous cell carcinoma (OSCC) in response to direct or indirect contact with SCC cells in comparison to results obtained in the cells of healthy subjects. To fulfill study objectives CAL 27 cell line and blood were obtained from cancer patients and control subjects. Parameters related to NETs formation were analyzed utilizing flow cytometry, fluorescence microscopy, and ELISA-type tests. The expression of selected phosphorylated proteins of the PI3K/Akt/PBK pathway in neutrophils was evaluated using the Western blot method. An increase in NETs formation was observed in a coculture of neutrophils with SCC cells, with the largest amount of NETs formed after stimulation with a supernatant obtained from the SCC culture. The enhanced process of NETs formation was accompanied by changes in the expression of proteins from the PI3K/Akt/PBK pathway. The obtained results prove the existence of interactions between neutrophils and cancer cells resulting in NETosis with the participation of the PI3K/Akt/PBK pathway in patients with OSCC.