Therapeutic efficacy of lysophosphatidylcholine in severe infections caused by Acinetobacter baumannii.

Due to the significant increase in antimicrobial resistance of Acinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused by A. baumannii. A. baumannii ATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml of A. baumannii. The therapeutic efficacy of LPC against A. baumannii in murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused by A. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused by A. baumannii.

New insights into the role of the immune microenvironment in breast carcinoma.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

Immunohistochemical organization patterns of the follicular dendritic cells, myofibroblasts and macrophages in the human spleen--new considerations on the pathological diagnosis of splenectomy pieces.

There is reliable information about how changes in spleen histology are influenced by the relationship among B and T lymphocytes, macrophages, dendritic cells and myofibroblasts. Moreover, if it can be applied in the day-by-day pathology laboratory. This work intends to elucidate morpho-functional aspects of relationships of these cells in the different spleen compartments, how they are influenced by pathological conditions and how basic immunohistochemical techniques could optimize the histopathological diagnosis. We analyzed the usefulness of the monoclonal antibodies CD45RO, CD20, CD21, CD35, CD68, caldesmon, the smooth muscle alpha-actin type 1 (SMA-1) in 91 specimens. CD21(+) CD35(+) follicular dendritic cells were organized into three patterns in agreement with the immune condition of the lymphoid follicle. Smooth muscle alpha-actin type 1(+)and caldesmon(+)myofibroblasts draw two double rings: marginal-perifollicular and germinal-marginal. The latter is closely related to T-cells. CD68(+)red pulp macrophages had clear and linear configuration. The interruption of this CD68(+) linear pattern in splenic marginal zone lymphoma cases could be a criterion to differentiate it from reactive hyperplasia. CD45RO, CD20, CD21, CD68 and SMA-1 provide a basic and quality immunohistochemical battery for a better comprehension of the human spleen and could improve its histopathological diagnosis.