Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment.

CD4+ T helper (TH) cells are key regulators in the tumour immune microenvironment (TIME), mediating the adaptive immunological response towards cancer, mainly through the activation of cytotoxic CD8+ T cells. After antigen recognition and proper co-stimulation, naïve TH cells are activated, undergo clonal expansion, and release cytokines that will define the differentiation of a specific effector TH cell subtype. These different subtypes have different functions, which can mediate both anti- and pro-tumour immunological responses. Here, we present the dual role of TH cells restraining or promoting the tumour, the factors controlling their homing and differentiation in the TIME, their influence on immunotherapy, and their use as prognostic indicators.

Impact of no publicly accessible prenatal education programming on patients and their care providers: a descriptive qualitative study in Nova Scotia, Canada.

OBJECTIVE: Patients in Nova Scotia do not have access to public prenatal education programming. This study aimed to explore whether care providers find patients are uninformed or misinformed, and the impact of that on patients and their care providers with a focus on clinical outcomes, time, resources and informed decision-making. METHODS: Semistructured interviews were conducted with 13 care providers around Halifax and Cape Breton. An interview guide (supplemental) of open-ended questions was used for consistency. A descriptive qualitative approach was employed to describe the contents of the interviews. Each interview was audio-taped and transcribed verbatim by an interdependent transcriber. Transcripts were analysed using established techniques in qualitative descriptive research including coding, grouping, detailing and comparing the data using NVivo V.12 software. A co-coder (SS) independently coded two interviews for inter-rater reliability. RESULTS: The study revealed six themes: (1) concern for a significant population of Nova Scotians experiencing pregnancy, birth and postpartum uninformed and misinformed, (2) consequences for patients who are uninformed and misinformed, (3) more time and resources spent on care for patients who are uninformed or misinformed, (4) patients and their care providers need a publicly available education programme, particularly vulnerable populations, (5) emphasis on programme quality and disappointment with the programme previously been in place and (6) recommendations for an effective prenatal education programme for Nova Scotians. CONCLUSIONS: This study shows care providers believe a public prenatal education programme could improve health literacy in Nova Scotia. Patients are seeking health education, but it is not accessible to all and being uninformed or misinformed negatively impacts patients' experiences and outcomes. This study revealed excess time and resources are being spent on individualised prenatal education by care providers with high individual and system-wide cost and explored the complicated process of providing patient-centred care for people who are uninformed or misinformed.

Map kinase and PKC signaling pathways modulate NGF-mediated apoE transcription.

The present study assessed the mechanisms by which nerve growth factor (NGF) increased the level of apolipoprotein E (apoE) in PC12 cells. NGF (50ng/mL) significantly increased apoE protein levels following 72h of treatment. Similarly NGF increased luciferase activity in cells transfected with a luciferase reporter construct containing a 500bp fragment of the apoE promoter, indicating NGF-induced apoE expression is regulated, at least in part, at the level of transcription. The non-selective nitric oxide synthase (NOS) inhibitor N(É·)-nitro-L-arginine methylester (L-NAME; 20mM) did not attenuate the NGF-mediated increase in luciferase activity, while the inducible NOS inhibitor s-methylisothiourea (S-MIU; 2mM) partially attenuated this action of NGF. Inhibition of MAP kinase activation with 50µM U0126 or pre-treatment with the PKC inhibitor bisindolylmaleimide 1 (BIS-1; 10µM) prevented the NGF-mediated activation of the apoE promoter. Pre-treatment with the phospholipase C (PLC) inhibitor U73122 (5µM) partially inhibited the NGF-induced increase in luciferase activity while the Akt inhibitor LY294002 (10µM) had no effect. These data suggest NGF-induced apoE transcription requires MAP kinase and PKC activation and that these TrkA signaling pathways may be modulated by NO.

Interactions between microglia and T cells in multiple sclerosis pathobiology.

Brain-resident microglia and T lymphocytes recruited into the central nervous system both play important roles in the neuropathology of multiple sclerosis. The microglia and recruited T cells are in close proximity in lesions of multiple sclerosis and in animal models, suggesting their potential for interactions. In support, microglia and T cells express a number of molecules that permit their engagement. Here we describe the interactions between T cells and microglia and the myriad responses that can result. These interactions include antigen presentation by microglia to activate T cells, the T cell activation of microglia, their progressive stimulation of one another, and the production of injurious or neurotrophic outcomes in their vicinity. Important considerations for the future include the nature of the T helper cell subsets and the M1 and M2 polarized nature of microglia, as the interactions between different subsets likely result in particular functions and outcomes. That T cells and microglia are in proximity and that they interact in lesions in the central nervous system implicate them as modifiers of pathobiology in multiple sclerosis.