Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.

Type 1 regulatory (Tr1) T cells induced by enforced expression of IL-10 (LV-10) are being developed as a novel treatment for chemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft vs host disease while mediating graft vs leukemia (GvL) effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature. Overlaying the signatures of sensitive and resistant pAML onto the public NCI TARGET pAML dataset revealed that sensitive pAML clustered with M5 monocytic pAML and pAML with MLL rearrangement. Resistant pAML clustered with myelomonocytic leukemias and those bearing the core binding factor translocations inv(16) or t(8;21)(RUNX1-RUNX1T1). Furthermore, resistant pAML upregulated the membrane glycoprotein CD200, which binds to the inhibitory receptor CD200R1 on LV-10 cells. To examine if CD200 expression on target cells can impair LV-10 cell function, we overexpressed CD200 in myeloid leukemia cell lines ordinarily sensitive to LV-10 killing. Indeed, LV-10 cells degranulated less and killed fewer CD200-overexpressing cells compared to controls, indicating that pAML can utilize CD200 expression for immune evasion. Altogether, the majority of pAML are killed by LV-10 cells in vitro, supporting further LV-10 cell development as an innovative cell therapy for pAML.

The Effects of Mindfulness on Lactation: An Integrative Review.

Background: It is well-known that stress and high levels of cortisol can negatively impact lactation outcomes. Mindfulness techniques are also known to be effective at reducing stress, and there has been some research into the effects of these techniques on breastfeeding. However, there has not yet been an integrative review examining the outcomes of the research carried out on this subject in the past 10 years. Objectives: The objective of this integrative review was to assess the effect of mindfulness techniques on lactation. This includes the effects on maternal stress, both perceived and physiologic, milk composition and volume, as well as the effects on the infants. Methods: The electronic databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Scopus, and Cochrane were searched using the key terms "meditate, meditation, relaxation or mindfulness" and "breastfeeding or lactation." Results: Nine articles met the inclusion criteria. Six key themes were identified. Mindfulness techniques reduce perceived and physiologic maternal stress and increase infant growth, particularly in the late preterm early term infant population. Infant behavior was also impacted by maternal mindfulness techniques as well as maternal milk volume, expression, and breastfeeding/pumping frequency. However, the effectiveness of mindfulness techniques is dose dependent. Conclusions: Mindfulness techniques are a simple and practical tool for postpartum breastfeeding people that have the potential to improve both lactation and infant outcomes.