Systemic immunological profile of children with B-cell acute lymphoblastic leukemia: performance of cell populations and soluble mediators as serum biomarkers.

Background: Children with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease. Methods: Here, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay. Results: On D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters. Conclusion: Finally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.

A dual-role for IL-10: From leukemogenesis to the tumor progression in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer in the world, and accounts for 25% of all childhood cancers among children under 15 years of age. Longitudinal studies have shown that children with ALL are born with a deregulated immune response that, together with postnatal environmental exposures, favor the onset of the disease. In this context, IL-10, a key cytokine in the regulation of the immune response, presents itself as a paradoxical mediator, initially influencing the development of ALL through the regulation of inflammatory processes and later on the progression of malignancy, with the increase of this molecule in the leukemia microenvironment. According to the literature, this cytokine plays a critical role in the natural history of the disease and plays an important role in two different though complex scenarios. Thus, in this review, we explore the dual role of IL-10 in ALL, and describe its biological characteristics, immunological mechanisms and genetics, as well as its impact on the leukemia microenvironment and its clinical implications.

Exploring the Profile of Cell Populations and Soluble Immunological Mediators in Bothrops atrox Envenomations.

Bothrops atrox envenomations are common in the Brazilian Amazon. The venom of B. atrox is highly inflammatory, which results in severe local complications, including the formation of blisters. Moreover, there is little information on the immune mechanisms associated with this condition. Thus, a longitudinal study was carried out to characterize the profile of the cell populations and soluble immunological mediators in the peripheral blood and blisters in B. atrox patients s according to their clinical manifestations (mild and severe). A similar response in both B. atrox patient groups (MILD and SEV) was observed, with an increase in inflammatory monocytes, NKT, and T and B cells, as well as CCL2, CCL5, CXCL9, CXCL10, IL-1ß and IL-10, when compared with the group of healthy blood donors. After the administration of antivenom, the participation of patrolling monocytes and IL-10 in the MILD group was observed. In the SEV group, the participation of B cells was observed, with high levels of CCL2 and IL-6. In the blister exudate, a hyperinflammatory profile was observed. In conclusion, we revealed the involvement of cell populations and soluble mediators in the immune response to B. atrox envenomation at the local and peripheral level, which is related to the onset and extent of the inflammation/clinical manifestation.

The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications.

The leukemic microenvironment has a high diversity of immune cells that are phenotypically and functionally distinct. However, our understanding of the biology, immunology, and clinical implications underlying these cells remains poorly investigated. Among the resident immune cells that can infiltrate the leukemic microenvironment are myeloid cells, which correspond to a heterogeneous cell group of the innate immune system. They encompass populations of neutrophils, macrophages, and myeloid-derived suppressor cells (MDSCs). These cells can be abundant in different tissues and, in the leukemic microenvironment, are associated with the clinical outcome of the patient, acting dichotomously to contribute to leukemic progression or stimulate antitumor immune responses. In this review, we detail the current evidence and the many mechanisms that indicate that the activation of different myeloid cell populations may contribute to immunosuppression, survival, or metastatic dissemination, as well as in immunosurveillance and stimulation of specific cytotoxic responses. Furthermore, we broadly discuss the interactions of tumor-associated neutrophils and macrophages (TANs and TAMs, respectively) and MDSCs in the leukemic microenvironment. Finally, we provide new perspectives on the potential of myeloid cell subpopulations as predictive biomarkers of therapeutical response, as well as potential targets in the chemoimmunotherapy of leukemias due to their dual Yin-Yang roles in leukemia.

Severe tissue complications in patients of Bothrops snakebite at a tertiary health unit in the Brazilian Amazon: clinical characteristics and associated factors.

INTRODUCTION: Snakebites in the Brazilian Amazon are caused mostly by snakes from the Bothrops genus and envenomated patients may suffer from tissue complications. METHODS: This study aimed to identify risk factors for severe tissue complications (STC) in patients with Bothrops snakebite in the Amazonas state, Brazil. RESULTS: Snakebites that were classified as severe and affected female patients with comorbidities presented greater risks of developing STCs. In addition, hospitalizations of patients with STC exceeded 5 days. CONCLUSIONS: Clinical and epidemiological characteristics can prove essential for assessing the evolution of STC and clinical prognosis of patients with Bothrops snakebites.

Severe tissue complications in patients of Bothrops snakebite at a tertiary health unit in the Brazilian Amazon: clinical characteristics and associated factors

Abstract INTRODUCTION: Snakebites in the Brazilian Amazon are caused mostly by snakes from the Bothrops genus and envenomated patients may suffer from tissue complications. METHODS: This study aimed to identify risk factors for severe tissue complications (STC) in patients with Bothrops snakebite in the Amazonas state, Brazil. RESULTS: Snakebites that were classified as severe and affected female patients with comorbidities presented greater risks of developing STCs. In addition, hospitalizations of patients with STC exceeded 5 days. CONCLUSIONS: Clinical and epidemiological characteristics can prove essential for assessing the evolution of STC and clinical prognosis of patients with Bothrops snakebites.