Extracellular vesicles released by myeloid-derived suppressor cells from pregnant women modulate adaptive immune responses.

Immunological pregnancy complications are a main challenge in reproductive medicine. Mechanisms regulating the adaptation of the maternal immune system to pregnancy are incompletely understood and therapeutic options limited. Myeloid derived suppressor cells (MDSC) are immune-modulatory cells expanding during healthy pregnancy and seem to play a crucial role for maternal-fetal tolerance.

Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and Modulate T-Cell and Monocyte Function.

Nosocomial bacterial infections (NBI) and necrotizing enterocolitis (NEC) are among the main reasons for death in preterm infants. Both are often caused by bacteria coming from the infected infant's gut and feeding with breast milk (BM) seems beneficial in their pathogenesis. However, mechanisms causing the protective effect of BM are only incompletely understood.

HLA-G promotes myeloid-derived suppressor cell accumulation and suppressive activity during human pregnancy through engagement of the receptor ILT4.

Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy.

Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses.

Immune tolerance toward the semiallogeneic fetus plays a crucial role in the maintenance of pregnancy. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their ability to modulate T-cell responses. Recently, we showed that MDSCs accumulate in cord blood of healthy newborns, yet their role in materno-fetal tolerance remained elusive.

[Screening for mental stress and the wish for psychological support in patients with breast cancer].

Objectives: The study explores whether breast-cancer patients who request psychosocial support have higher psychological strain compared to those who do not. We also explored whether scores on HADS-D and PHQ-D identify the same patients as being stressed as well as the relationship between patient's wish for psychological support and psychological strain.

Methods: 115 inpatients with breast cancer took part in the screening and were asked if they wanted psychosocial support.

Loss of Drop1 expression already at early tumor stages in a wide range of human carcinomas.

In a study on gene deregulation in ovarian carcinoma we found a mRNA coding for a 350 kDa protein, Drop1, to be downregulated 20- to 180-fold in the majority of ovarian and mammary carcinomas. The mRNA is encoded by a set of exons in the 5' region of the SYNE1 gene. Immunohistochemical staining for Drop1 protein by a specific monoclonal antibody corresponds to the pattern seen for the mRNA.

A stable niche supports long-term maintenance of human epidermal stem cells in organotypic cultures.

Stem cells in human interfollicular epidermis are still difficult to identify, mainly because of a lack of definitive markers and the inability to label human beings for label-retaining cells (LRCs). Here, we report that LRCs could be identified and localized in organotypic cultures (OTCs) made with human cells. Labeling cultures for 2 weeks with iododeoxyuridine (IdU) and then chasing for 6-10 weeks left <1% of basal cells retaining IdU label.

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors.

Background: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon.

Material And Methods: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo.

Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer.

Purpose: Ertumaxomab is an intact bispecific antibody targeting HER2/neu and CD3 with selective binding to activatory Fcgamma type I/III receptors, resulting in the formation of a tri-cell complex between tumor cells, T cells, and accessory cells. Patients with metastatic breast cancer were enrolled into a multicenter phase I dose-escalating trial.

Experimental Design: Three ascending doses of ertumaxomab (10-200 microg) were administered i.

Glucocorticoid-mediated inhibition of chemotherapy in ovarian carcinomas.

The glucocorticoid dexamethasone is frequently used as a co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons.

L1 on ovarian carcinoma cells is a binding partner for Neuropilin-1 on mesothelial cells.

The progression of ovarian cancer is driven by a variety of cellular factors that are incompletely understood. Binding of tumor cells to normal cells and to soluble factors influence tumor growth, angiogenesis and the stimulation of vascular permeability leading to ascites production. L1 adhesion molecule is overexpressed in ovarian carcinoma and is associated with bad prognosis.

Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers.

Purpose: There is evidence that some tumor patients are able to generate tumor-associated antigen (TAA)-specific T-cell immunity spontaneously. However, little is understood about the existence and nature of self-reactive T-cells that recognize TAA in healthy donors (HD).

Methods: Human mucin (MUC-1), a highly glycosylated transmembrane protein, is a well characterized TAA expressed by epithelial tumors.

Preeclampsia: increased expression of soluble ADAM 12.

Preeclampsia is a multisystemic pregnancy-associated disease affecting about 3-7% of pregnancies worldwide and is still a principal cause of fetal and maternal morbidity and mortality. To identify potential markers, we have compared gene expression profiles from control and preeclamptic placental tissues taken at various age-matched gestational stages using complementary DNA microarray analysis. Besides previously identified preeclampsia-associated genes, novel differentially expressed transcripts were found.

Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells.

Purpose: The L1 adhesion molecule (CD171) is overexpressed in human ovarian and endometrial carcinomas and is associated with bad prognosis. Although expressed as a transmembrane molecule, L1 is released from carcinoma cells in a soluble form. Soluble L1 is present in serum and ascites of ovarian carcinoma patients.

A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.

Adjuvant treatment is still only working in a small percentage of breast cancer patients. Therefore, new strategies need to be developed. Immunotherapies are a very promising approach because they could successfully attack tumor cells in the stage of dormancy.

Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAMxCD64 (HEA125x197) bispecific antibody.

Bispecific antibodies (bsAb) have attracted much attention over the past several years as a mean to improve immunotherapy of cancer. Due to their dual specificity, bsAb are able to redirect effector cells against tumor targets. In this study, the development and preclinical testing of a new quadroma-derived bsAb, HEA125x197, recognizing the tumor-associated Ep-CAM antigen and the high affinity Fc receptor for IgG, CD64, is reported.

Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma.

Bispecific antibody HEA125 x OKT3 was shown to redirect T lymphocytes toward carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have demonstrated that tumor-associated lymphocytes (TAL) derived from malignant ascites can be used as effector cells with a high efficacy and without prior stimulation. These data provided the rationale for a clinical trial to investigate whether bsAb HEA125 x OKT3 is also able to induce tumor cell lysis in vivo and can be used for local treatment of malignant ascites arising from ovarian carcinoma.