Purpose: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4 + T cell numbers and function. We have previously shown that increased regulatory T cell (T reg ) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model. Experimental Design: A monoclonal antibody (9H10) to CTLA-4 was employed against wellestablished glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4 + T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4 + CD25À responderTcells were evaluated. Results: CTLA-4 blockade confers long-term survival in 80 % of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4 À T cells from treated mice show improved proliferative responses and resistance to T reg -mediated suppression, whereas T regs from the same mice remain anergic and exhibit no restriction of their suppressive capacity. Conclusions: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance toT reg -mediated suppression, and not through direct effects onT regs .

Purpose: Elevated proportions of regulatory T cells (T reg ) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examinedT regs in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. + T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25 + cells but fails to completely eliminate T regs , reducing their number only moderately, yet eliminating their suppressive function. This elimination of T reg function permits enhanced lymphocyte proliferative and IFN-g responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis. Conclusions: Systemic anti-CD25 administration does not entirely eliminateT regs but does prevent T reg function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T reg compartments seen in patients with malignant glioma.

Assessing hospital environment conditions is necessary for healthcare providers and patients to coordinate safe care. The aims of this research included: a) identifying patterns in hospital visit feedback transcripts regarding bathroom doors and lights in the hospital room and b) interpreting the results to make recommendations for more enabling clinical environments. The methods used by the research team included organizing transcript data, assigning codes, and conducting an interrater reliability test to assess codebook efficacy. Finally, working with maternal and infant mortality experts, recommendations for the hospital were developed. We identified four possible interventions to address barriers: a) implement low-height, dimmable lighting along the base of the patient room, b) provide personal lights, such as penlights, to staff for nighttime assessments, c) install and improve on existing grab bars in patient room bathrooms and d) replace the standard patient room bathroom door with a different kind of auditory/visual privacy barrier.