The elementome of calcium-based urinary stones and its role in urolithiasis

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components. Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective. Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity. The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns. Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation. The elementome - the full spectrum of elemental content - of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease

Myeloid-Derived Suppressor Cells in Tumor-Induced T Cell Suppression and Tolerance

Tumor development is often associated with a deep alteration of normal myelopoiesis, leading to a progressive accumulation of various cellular elements, belonging to myelomonocytic lineage, in the tumor bed, in the blood, and in both primary and secondary lymphoid organs. This heterogeneous pool of cells expresses, in the mouse, the common markers CD11b and Gr-1 (Ly6C/G) and is endowed with the ability to suppress antigen and/or polyclonal-driven T cell immune response. These cells, named myeloid-derived suppressor cells (MDSCs), are mobilized from hematopoietic organs by cytokines and other factors produced by the tumors, as well as by strong activation of the immune system, and have a profound influence on the outcome of the T cell-dependent immune responses. MDSCs can restrain T cell function directly in an antigen-independent manner; however, in vivo, MDSCs can also process and present tumor-associated antigen and can lead to T cell tolerance in an antigen-specific manner. Furthermore, MDSCs seem to be key players in tumor-induced suppressive network that includes T regulatory (Treg) cells, inhibitory natural killer T (NKT) cells, mast cells, Th17, as well as effector T cells. The importance of MDSCs in human malignancies has been demonstrated in recent years and new approaches targeting their suppressive/tolerogenic action are currently being tested in both preclinical model and clinical trials