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Abstract

Within chronic lymphocytic leukemia (CLL) patients, increased expression of the exhaustion marker PD-1 and the activation marker HLA-DR by CD4+ T cells is indicative of disease progression and associates with poor outcomes. Physical activity (PA) may slow disease progression. Whether PA impacts CD4+ T cell phenotype in CLL patients is unknown. PURPOSE: To compare the proportion of HLA-DR+PD-1+ CD4+ T cells in CLL patients before and after 4 months of interventions designed to increase PA. METHODS: CLL patients (N=24) within 3 months of diagnosis were entered into a 4-month exercise training program consisting of at-home aerobic and/or resistance training exercises with remote coaching. Blood samples were collected at baseline and 4 months. Batch analyses of frozen peripheral blood mononuclear cells (PBMCs) were conducted via flow cytometry. Fluorescent antibodies for CD3, CD4, CD8, HLA-DR, and PD-1 were used to identify T-cell subsets. CD4+ T cell phenotypes were compared at baseline and 4 months via Wilcoxon signed-rank test. RESULTS: The proportion of CD4+ T cells (% of total T cells) did not differ from baseline (pre) to month 4 (post): pre: (mean ± SD) 59.25 ± 16.75 vs. post: 60.05 ± 13.78; z = -0.314, p = 0.753. CD4+ T cell subset proportions (% of CD4 T cells) also did not differ pre to post: CD4+HLA-DR+ pre: 6.08 ± 3.50 vs. post: 6.63 ± 4.79; z = -0.071, p = 0.943, CD4+PD1+pre: 33.30 ± 19.00 vs. post: 33.33 ± 18.38; z = -0.086, p = 0.932, and CD4+HLA-DR+PD1+ pre: 3.70 ± 2.12 vs. post: 3.91 ± 2.43; z = -0.157, p = 0.875. CONCLUSION: PA intervention did not result in a significant change in CD4+ T cell phenotypes at 4 months relative to baseline. Future studies should account for varying rates of adherence to the prescribed PA interventions as well as comorbidity. Additional lymphocyte characteristics associated with disease progression, such as CD4:CD8 ratio, should also be investigated.

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