Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and relatively indolent B-cell lymphoma. Characteristically, the [lymphocyte-predominant (LP)] tumor cells are embedded in a microenvironment enriched in lymphocytes. More aggressive variants of mature B-cell and peripheral T-cell lymphomas exhibit nuclear expression of the polo-like kinase 1 (PLK1) protein, stabilizing MYC (alias c-myc) and associated with worse clinical outcomes. This study demonstrated expression of PLK1 in the LP cells in 100% of NLPHL cases (n = 76). In contrast, <5% of classic Hodgkin lymphoma cases (n = 70) showed PLK1 expression within the tumor cells. Loss-of-function approaches demonstrated that the expression of PLK1 promoted cell proliferation and increased MYC stability in NLPHL cell lines. Correlation with clinical parameters revealed that the increased expression of PLK1 was associated with advanced-stage disease in patients with NLPHL. A multiplex immunofluorescence panel coupled with artificial intelligence algorithms was used to correlate the composition of the tumor microenvironment with the proliferative stage of LP cells. The results showed that LP cells with PLK1 (high) expression were associated with increased numbers of cytotoxic and T-regulatory T cells. Overall, the findings demonstrate that PLK1 signaling increases NLPHL proliferation and constitutes a potential vulnerability that can be targeted with PLK1 inhibitors. An active immune surveillance program in NLPHL may be a critical mechanism limiting PLK1-dependent tumor growth.

Feasibility and Preliminary Safety of Smartphone-Based Automated Insulin Delivery in Adolescents and Children With Type 1 Diabetes.

BACKGROUND: A smartphone-based automated insulin delivery (AID) controller device can facilitate use of interoperable components and acceptance in adolescents and children. METHODS: Pediatric participants (N = 20, 8F) with type 1 diabetes were enrolled in three sequential age-based cohorts: adolescents (12-<18 years, n = 8, 5F), school-age (8-<12 years, n = 7, 2F), and young children (2-<8 years, n = 5, 1F). Participants used the interoperable artificial pancreas system (iAPS) and zone model predictive control (MPC) on an unlocked smartphone for 48 hours, consumed unrestricted meals of their choice, and engaged in various unannounced exercises. Primary outcomes and stopping criteria were defined using fingerstick blood glucose (BG) data; secondary outcomes compared continuous glucose monitoring (CGM) data with preceding sensor augmented pump (SAP) therapy. RESULTS: During AID, there was no more than one BG <50 mg/dL except in one young child participant; no instance of more than two episodes of BG ≥300 mg/dL lasting longer than 2 hours; and no adverse events. Despite large meals (total of 404.9 grams of carbs) and unannounced exercise (total of 182 minutes), overall CGM percent time in range (TIR) of 70 to 180 mg/dL during AID was statistically similar to SAP (63.5% vs 57.3%, respectively, P = .145). Overnight glucose standard deviation was 43 mg/dL (vs SAP 57.9 mg/dL, P = .009) and coefficient of variation was 25.7% (vs SAP 34.9%, P < .001). The percent time in closed-loop mode and connected to the CGM was 92.7% and 99.6%, respectively. Surveys indicated that participants and parents/guardians were satisfied with the system. CONCLUSIONS: The smartphone-based AID was feasible and safe in sequentially younger cohorts of adolescents and children. CLINICALTRIALS.GOV: NCT04255381 (https://clinicaltrials.gov/ct2/show/NCT04255381).