Detecting Prostate Cancer Using Pattern Recognition Neural Networks With Flow Cytometry-Based Immunophenotyping in At-Risk Men.

Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry-based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls.

Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs.

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM).

Unique pattern of neutrophil migration and function during tumor progression.

Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant, uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancer exhibited much more spontaneous migration than that of control neutrophils from tumor-free mice. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and increased production of ATP, relative to that of control neutrophils.

CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients.

Background: Myeloid-derived suppressor cells (MDSCs) are a population of immature immune cells with several protumorigenic functions. CD38 is a transmembrane receptor-ectoenzyme expressed by MDSCs in murine models of esophageal cancer. We hypothesized that CD38 could be expressed on MDSCs in human colorectal cancer (CRC), which might allow for a new perspective on therapeutic targeting of human MDSCs with anti-CD38 monoclonal antibodies in this cancer.

Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses in cancer and have been directly implicated in promotion of tumor progression. However, the heterogeneity of these cells and lack of distinct markers hampers the progress in understanding of the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation we determined that low density PMN-MDSC and high density neutrophils from the same cancer patients had a distinct gene profile.

Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody.

Myeloid-derived suppressor cells (MDSC) are one of the major contributors to immune suppression in cancer. We recently have demonstrated in preclinical study that MDSCs are sensitive to TRAIL receptor 2 (TRAIL-R2) agonist. The goal of this study was to clinically test the hypothesis that targeting TRAIL-R2 can selectively eliminate MDSCs.

The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged.

T-lymphocyte migration is important for homing, cell trafficking, and immune surveillance. T-lymphocytes express lymphocyte function-associated antigen-1 (LFA-1; αLβ2) and very late antigen-4 (VLA-4; α4β1), which bind to their cognate ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These adhesive interactions provide T-lymphocytes with the ability to withstand hemodynamic shear forces to facilitate adhesion and migration along the blood endothelium.

Effect of adhesion and chemokine presentation on T-lymphocyte haptokinesis.

Motility is critical for the function of T-lymphocytes. Motility in T-lymphocytes is driven by the occupancy of chemokine receptors by chemokines, and modulated by adhesive interactions. However, it is not well understood how the combination of adhesion and chemokine binding affects T-lymphocyte migration.

Diffuse photon density wavefront speed as a contrast for tomographic imaging of heterogeneous diffusive media.

An imaging algorithm is implemented for tomographically reconstructing contrast maps of the space variant speed of diffuse photon density wavefronts (DPDWFs) propagating in biological tissue-like diffusing media. This speed serves as a novel contrast not previously exploited in the literature. The algorithm employs early photon arrival times (EPATs) extracted from a set of time domain measurements.