Measuring Pro- and Anti-Inflammatory Biomarkers Among Low-Income Hispanic Adults: A Feasibility and Pilot Assessment

Using the Orsmond and Cohen feasibility framework, the primary aim of this study was to assess the feasibility of the implementation of recruitment strategies, data collection procedures, and managerial resources needed to assess pro- and anti-inflammatory biomarkers from low-income, younger Hispanic adults. The secondary aim of this study was to describe the relationship between discrimination stress and inflammation as pilot work for future studies. Data were collected in a Houston-area community center from self-identifying Hispanic adults (ages 21–35) (August 2018). Inflammation was evaluated from blood samples, and interviewer-administered surveys in participants’ preferred language measured discrimination stress (Hispanic Stress Inventory-2 discrimination subscale). Spearman rank-order correlations evaluated the relationships between discrimination stress and inflammatory biomarkers. The recruitment strategies, data collection strategy, and the associated resources were evaluated and found to be feasible. While 50 participants consented to donate blood, five were too dehydrated for sample collection. Among the 45 participants [Mage = 28.9 (SD = 4.4), 17.8% U.S.-born, 42.2% 1.5 generation, 40% 1.0 generation], discrimination stress was negatively correlated with proinflammatory cytokine interleukin-8 (p \u3c 0.01). This study demonstrated feasibility using established benchmarks. The negative correlation between discrimination stress and interleukin-8 suggests discrimination stress may contribute to inflammatory dysregulation

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice

BackgroundEvery bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from healthy volunteers at rest and at the end of an acute bout of cycling exercise. Flow cytometry and single-cell RNA sequencing was performed to identify phenotypic and transcriptomic differences between resting and exercise-mobilized cells using a targeted gene expression panel curated for human immunology. PBMCs were injected into the tail vein of xenogeneic NSG-IL-15 mice and subsequently challenged with a luciferase tagged chronic myelogenous leukemia cell line (K562). Tumor growth (bioluminescence) and xenogeneic graft-versus-host disease (GvHD) were monitored bi-weekly for 40-days.ResultsExercise preferentially mobilized NK-cell, CD8+ T-cell and monocyte subtypes with a differentiated and effector phenotype, without significantly mobilizing CD4+ regulatory T-cells. Mobilized effector lymphocytes, particularly effector-memory CD8+ T-cells and NK-cells, displayed differentially expressed genes and enriched gene sets associated with anti-tumor activity, including cytotoxicity, migration/chemotaxis, antigen binding, cytokine responsiveness and alloreactivity (e.g. graft-versus-host/leukemia). Mice receiving exercise-mobilized PBMCs had lower tumor burden and higher overall survival (4.14E+08 photons/s and 47%, respectively) at day 40 compared to mice receiving resting PBMCs (12.1E+08 photons/s and 22%, respectively) from the same donors (p<0.05). Human immune cell engraftment was similar for resting and exercise-mobilized DLI. However, when compared to non-tumor bearing mice, K562 increased the expansion of NK-cell and CD3+/CD4-/CD8- T-cells in mice receiving exercise-mobilized but not resting lymphocytes, 1-2 weeks after DLI. No differences in GvHD or GvHD-free survival was observed between groups either with or without K562 challenge.ConclusionExercise in humans mobilizes effector lymphocytes with an anti-tumor transcriptomic profile and their use as DLI extends survival and enhances the graft-versus-leukemia (GvL) effect without exacerbating GvHD in human leukemia bearing xenogeneic mice. Exercise may serve as an effective and economical adjuvant to increase the GvL effects of allogeneic cell therapies without intensifying GvHD