Pattern and Prevalence of Liver Involvement in Pediatric Acute Lymphoblastic and Myeloid Leukemia at Diagnosis.

Objectives: The prevalence and significance of liver involvement at diagnosis was studied in pediatric acute lymphoblastic (ALL) and myeloid leukemia (AML).

Methods: A population based cohort of 122 pre B-ALL, 22 T-ALL and 45 AML patients was formed from the Nordic Society of Pediatric Hematology and Oncology leukemia registries (years 2005-2017). Hepatomegaly, elevated alanine aminotransferase, high INR, hypoalbuminemia and conjugated hyperbilirubinemia at diagnosis were used as markers for liver involvement.

Low Expression of miR-18a as a Characteristic of Pediatric Acute Lymphoblastic Leukemia.

Background: Acute lymphoblastic leukemia (ALL) occurs in both adults and children but the response to chemotherapy and survival is significantly worse in the adults. We aimed to study whether the expression of immune system-associated miRNAs would differ between adult and pediatric patients with ALL at the time of diagnosis.

Materials And Methods: Inflammation-associated miRNA analysis was performed in 19 adults and 79 pediatric patients with ALL and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339.

Detection of Group A Streptococcus from Pharyngeal Swab Samples by Bacterial Culture Is Challenged by a Novel mariPOC Point-of-Care Test.

mariPOC is a novel point-of-care test system for rapid detection of respiratory tract infections. We compared the performance of the mariPOC test to that of bacterial culture for detecting group A streptococcus (GAS) in 219 pharyngitis patients (ages 1-64 years) and 109 healthy asymptomatic controls (ages 19-69 years). In addition, 42 patient samples were analyzed by quantitative PCR (qPCR).

Dasatinib promotes Th1-type responses in granzyme B expressing T-cells.

Tyrosine kinase inhibitors (TKIs) have dramatically improved the outcome of chronic myeloid leukemia (CML). Besides inhibiting target kinases in leukemic cells, 2nd generation TKI dasatinib also inhibits off-targets in immune effector cells resulting in atypical immune responses in some patients. Dasatinib has been described to increase the proportion of late effector memory T-cells, however, to date no follow-up studies have been performed in first-line patients.

Enlarged memory T-cell pool and enhanced Th1-type responses in chronic myeloid leukemia patients who have successfully discontinued IFN-α monotherapy.

A small proportion of chronic myeloid leukemia patients treated with interferon-α (IFN-α) monotherapy are able to discontinue the treatment without disease relapse although residual leukemia cells are present. Recently, we showed that these patients have increased amount of NK-cells and a distinct blood cytokine profile. We now aimed to study the function of NK- and T-cells in order to understand the role of the immune system in maintaining the treatment response after IFN-α discontinuation.

Imatinib and pegylated IFN-α2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response.

Objectives: Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-α2b) and imatinib may increase the rate of successful discontinuation.

Methods: In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg-IFN-α2b.

Dendritic cells from Crohn's disease patients show aberrant STAT1 and STAT3 signaling.

Abnormalities of dendritic cells (DCs) and STAT proteins have been reported in Crohn's disease (CD). Studies on JAK/STAT signaling in DCs are, however, lacking in CD. We applied a flowcytometric single-cell-based phosphoepitope assay to evaluate STAT1 and STAT3 pathways in DC subsets from CD patients.

The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease.

Background: Chemokine receptor CXCR4, together with its ligand CXCL12, plays critical roles in cancer progression, including growth, metastasis and angiogenesis. Ewing sarcoma is a sarcoma with poor prognosis despite current therapies, particularly for patients with advanced-stage disease. Lungs and bone (marrow), organs of predilection for (primary/metastatic) Ewing sarcoma, represent predominant CXCL12 sources.

The presence of sinusoidal CD163(+) macrophages in lymph nodes is associated with favorable nodal status in patients with breast cancer.

As macrophages are some of the first cells to encounter metastatic tumor cells in sentinel lymph nodes (SLN) and natural killer (NK) cells are critical to the cytotoxicity of abnormal cells, we sought to determine if these cell populations were altered in the presence of nodal metastasis. We used immunohistochemistry to assess the SLN of 47 patients with breast cancer (36 with nodal metastasis and 11 without nodal metastasis) and 10 control lymph nodes. We assessed metastatic areas and nonmetastatic areas separately for CD163, a marker of macrophages, and ANK-1, a marker for precursors of activated NK cells.

Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes.

Objective: Dendritic cells (DCs) are largely responsible for the activation and fine-tuning of T-cell responses. Altered numbers of blood DCs have been reported in type 1 diabetes (T1D). We aimed at characterizing the less well-known phenotypic properties of DCs in T1D.

High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.

Background. Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system-related genes are activated and have prognostic significance in Ewing's sarcoma family of tumors (ESFTs).

Metastasis to sentinel lymph nodes in breast cancer is associated with maturation arrest of dendritic cells and poor co-localization of dendritic cells and CD8+ T cells.

The regional immune systems of patients with breast cancer are immunosuppressed. Dendritic cells are professional antigen-presenting cells and present cancer-associated antigens to the adaptive immune system in sentinel lymph nodes. Dendritic cells may promote, or inhibit, an adaptive immune response to specific antigens.

Chronic myeloid leukemia patients in prolonged remission following interferon-α monotherapy have distinct cytokine and oligoclonal lymphocyte profile.

Before the era of tyrosine kinase inhibitors (TKIs), interferon-alpha (IFN-α) was the treatment of choice in chronic myeloid leukemia (CML). Curiously, some IFN-α treated patients were able to discontinue therapy without disease progression. The aim of this project was to study the immunomodulatory effects of IFN-α in CML patients in prolonged remission and isolate biological markers predicting response.

Poor cytokine-induced phosphorylation in chronic myeloid leukemia patients at diagnosis is effectively reversed by tyrosine kinase inhibitor therapy.

Objective: In chronic myeloid leukemia (CML), uncontrolled tyrosine kinase activity of the BCR-ABL1 oncoprotein results in aberrant signaling pathways and increased cell proliferation. Acquired immune tolerance to leukemic antigens further enables tumor cell expansion. Tyrosine kinase inhibitor (TKI) therapy interferes with the immunoregulatory system by targeting off-target kinases both in malignant and nonmalignant cells.

Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer.

Background: There is evidence that the immune systems of patients with breast cancer are dysfunctional. Regulatory T cells (Tregs), and IDO, an immunosuppressive enzyme, are associated with more advanced disease in some cancers and may promote immunologic tolerance to tumors. Our aim was to assess whether expression of Foxp3, a marker of Tregs, and IDO were linked with nodal metastasis in breast cancer patients.

Pediatric cancers are infiltrated predominantly by macrophages and contain a paucity of dendritic cells: a major nosologic difference with adult tumors.

Purpose: Adult cancer is frequently preceded by a period of prolonged chronic inflammation caused by infectious microbial agents or physical or chemical irritants. By contrast, an association between the classic pediatric neoplasias and inflammatory triggers is only rarely recognized. We hypothesized that the difference could be reflected in the inflammatory cell infiltrates of pediatric and adult cancer.

Imaging analysis of STAT1 and NF-kappaB translocation in dendritic cells at the single cell level.

Rapid assessment of immune or stem cells, which are now widely applied in the clinical setting of cancer treatment, is necessary to speed their development and to determine their quality. We have evaluated immature dendritic cells (iDC) by semiautomated imaging cytometry which provides detailed assessment at a single cell level. Nuclear translocation of NF-kappaB was studied by imaging analysis as well as electrophoretic mobility shift assay with an excellent correlation (r = 0.

A basis for distinguishing cultured dendritic cells and macrophages in cytospins and fixed sections.

There is a burgeoning literature on the contrasting role of intratumoral dendritic cells (DCs) and tumor-associated macrophages, making reliable identification of both cell types in clinical and experimental tissue sections important. However, because these cell types are closely related and share several differentiation antigens, their absolute distinction in tissue sections is difficult. We differentiated DCs and macrophages from monocytes in vitro, prepared cytospins and paraffin-embedded sections of the various cell populations, and tested a variety of antibodies that purportedly recognize monocytes and DCs for their capacity to react and distinguish cells after conventional formalin fixation.

Imaging analysis of STAT1 and NF-kappaB translocation in dendritic cells at the single cell level.

Rapid assessment of immune or stem cells, which are now widely applied in the clinical setting of cancer treatment, is necessary to speed their development and to determine their quality. We have evaluated immature dendritic cells (iDC) by semiautomated imaging cytometry which provides detailed assessment at a single cell level. Nuclear translocation of NF-kappaB was studied by imaging analysis as well as electrophoretic mobility shift assay with an excellent correlation (r=0.

A novel epitope of N-CAM defines precursors of human adherent NK cells.

Activated, adherent natural killer (A-NK) cells represent a distinct subpopulation of interleukin (IL)-2-stimulated NK cells, which are selectively endowed with the increased expression of integrins and ability to adhere to solid surfaces, migrate into, infiltrate, and destroy cancerous tissues. The present study defines the phenotype and functions of precursors of A-NK (pre-A-NK) cells in humans. Peripheral blood pre-A-NK cells, in contrast to the rest of NK cells, express a novel epitope of CD56 neuronal cell adhesion molecule, termed ANK-1, and increased cell-surface levels of integrins.