Citations

The expansion and accumulation of HIV-infected BCL6 + Tfh CD4 + T cells are thought to contribute to the persistence of viral reservoirs in infected subjects undergoing ART. Two mechanisms have been raised for the preferential retention of HIV within Tfh CD4 + T cells: (i) antiretroviral drugs have limited tissue distribution, resulting in insufficient tissue concentration and lower efficacy in controlling HIV replication in lymphoid tissues, and (ii) cytotoxic CD8 + T cells within lymphoid tissues express low levels of chemokine receptor (CXCR5), thus limiting their ability to enter the GCs to control/eliminate HIV-infected Tfh cells. Our results indicate that the BCL6 inhibitor FX1 can not only repress HIV infection of tonsillar Tfh ex vivo but also suppress HIV infection and reactivation in primary, non-Tfh CD4 + T cells. Our study provides a rationale for targeting BCL6 protein to extend ART-mediated reduction of persistent HIV and/or support strategies toward HIV remission beyond ART cessation.

Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune response, flexible electrodes under 10 µm in diameter have been proposed as ideal next-generation neural interfaces. However, the representation of motion artifact during neurochemical or electrophysiological recordings using ultra-small, flexible electrodes remains unexplored. In this short communication, we characterize motion artifact generated by the movement of 7 µm diameter carbon fiber electrodes during electrophysiological recordings and fast-scan cyclic voltammetry (FSCV) measurements of electroactive neurochemicals. Through in vitro and in vivo experiments, we demonstrate that artifact induced by motion can be problematic to distinguish from the characteristic signals associated with recorded action potentials or neurochemical measurements. These results underscore that new electrode materials and recording paradigms can alter the representation of common sources of artifact in vivo and therefore must be carefully characterized.

9090 Background: We identified factors associated with better OS for previously treated, PD-L1–expressing advanced NSCLC using data from KEYNOTE-010 (NCT01905657; Herbst et al. Lancet. 2016;387:1540-50), in which pembrolizumab had superior OS over docetaxel. Methods: 1033 patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel 75 mg/m2 Q3W. Response was assessed per RECIST v1.1 by independent central review. Multivariate analyses were performed using a Cox proportional hazards regression model on OS in the pembrolizumab arms. A set of variable selection methods was applied to 19 baseline demographic and disease characteristics, including smoking status, and identified 7 factors that contributed to OS. Data cut was September 30, 2016. Results: Adjusted hazard ratios (HRs) for the factors in the pembrolizumab arm from the model are shown in the Table. Updated OS with an additional 6 months of follow-up from this data lock for KEYNOTE-010 will be presented. Conclusions: While the overall result of KEYNOTE-010 revealed improved OS with pembrolizumab compared with docetaxel in previously treated patients with PD-L1–positive advanced NSCLC, exploratory, post hoc multivariate analyses showed that some laboratory and tumor characteristics such as nonsquamous histology, normal baseline lactate dehydrogenase (LDH), PD-L1 TPS ≥50%, and wild-type EGFR mutation status were associated with better OS among patients treated with pembrolizumab. Clinical trial information: NCT01905657. [Table: see text]