Immunotherapies based on PD-1/PD-L1 pathway inhibitors in ovarian cancer treatment.

Immunotherapies based on anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway inhibitors may turn out effective in ovarian cancer (OC) treatment. They can be used in combination with standard therapy and are especially promising in recurrent and platinum-resistant OC. There is growing evidence that the mechanism of the PD-1/PD-L1 pathway can be specific for a particular histological cancer type. Interestingly, the data have shown that the PD-1/PD-L1 pathway blockade may be effective, especially in the endometrioid type of OC. It is important to identify the cause of anti-tumor immune response suppression and exclude its other mechanisms in OC patients. It is also necessary to conduct subsequent studies to confirm in which OC cases the treatment is effective and how to select patients and combine drugs to improve patient survival.

Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells.

PURPOSE: The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS: Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83- phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS: We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.

Psychological mindedness and abstract reasoning in late childhood and adolescence: An exploration using new instruments.

This study introduces two new measures of psychological mindedness, applying them in a study of the growth of abstract thinking in children and adolescents in a developmental design. The capacity to achieve psychological understanding of the self and of others involves comprehension of the motives, attitudes, and characteristics of the self and others. Psychological mindedness toward the self (PS) and toward others (PO) may be seen as complex cognitive capacities that should show a pattern of related development in childhood. Three groups of 60 fifth, eighth, and twelfth graders completed two measures of formal operations and two instruments to assess the two components of psychological mindedness. We find that psychological mindedness and abstract thinking both increase significantly with age, although the relationship between them is complex and varies with gender and age. Because the development of abstract reasoning skills does not correlate with the development of psychological mindedness in a simple way, a more complex model is necessary, taking age and gender differences into account. Performance on the two measures of psychological mindedness is found to be largely unrelated, suggesting that these are two different psychological skills. Implications of these findings are discussed, with special reference to education, peer counseling, and psychotherapy.

Predictors of children's postdivorce adjustment.

Six hypotheses to explain how divorce may affect the trajectory of child development were tested using standardized measures and sociodemographic data. Correlational and multiple regression analyses revealed that the parent adjustment hypothesis received the strongest support. Boys appeared sensitive to events and behavior in their mothers' lives, while girls seemed attuned to mothers' internal states.

Perceptions of quality of life following divorce: a study of children's prognostic thinking.

The general quality of latency-aged children's prognostic thinking and the way in which they view the long-range impact of divorce upon peer adaptation are explored. When interviewed about responses to two fictional peers with marked behavior problems, 80 children in the third and fifth grades displayed an optimism in their prognostic thinking about the future of these peers. In general, peers from divorced homes were perceived as having a more positive future adjustment than peers from intact homes. However, male subjects from disrupted homes revealed a significantly pessimistic orientation regarding the impact of divorce upon the future; females from disrupted homes had a strikingly optimistic view. Implications for school-based interventions are discussed.