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To determine the impact of repeated panobinostat dosing on overall T cell activation, we evaluated the expression of the early T cell activation marker CD69 throughout the study ( Fig. Hence, a deeper understanding of the immunomodulatory effects of HDACi in nononcology patients is much needed to guide the potential development of HDACi for the treatment of other disease indications such as their use in anti-inflammatory and curative HIV strategies. However, the clear majority of clinical HDACi trials have been conducted in the oncology field, and those studies have offered little insight into immunological effects of HDACi treatment in patients without malignancy. Therefore, interpretation of preclinical data requires careful consideration and necessitates confirmation of findings in clinical trials. In fact, the overall effect of HDACi treatment on host immune pathways appears to vary with both the applied model system and the indication for which HDACi is administered. The latter observation might explain why contradictory results arise from in vitro models, animal models, and human studies. HDACi affect pathological tissue differently from normal tissue e.g., malignant cells are more sensitive to HDAC inhibition than nonmalignant cells, and antineoplasm effects dominate over immunomodulatory effects when both cell types are present in vivo ( 12). Importantly, measures of immune function returned to baseline after panobinostat treatment and follow-up revealed no sustained effect on overall gene expression. We found that proportions of CD4 + and CD8 + T cells expressing CD69 increased 24 h after initial panobinostat administration ( P 1.5 false-discovery-rate -corrected P, <0.05). Gene expression in purified peripheral blood mononuclear cells (PBMCs) was evaluated using an Affymetrix HTA 2.0 gene chip. Whole-blood stimulations were performed and cytokine responses measured using Luminex. Using flow cytometry, we investigated changes in T cell activation (CD69, CD38, HLA-DR) and the expression of CD39 and CTLA4 on regulatory T cells (Tregs). Therefore, we aimed to evaluate immunological effects of treatment with the HDACi panobinostat in HIV-infected patients during a clinical phase IIa latency reversal trial. Histone deacetylase inhibitors (HDACi) modulate the transcriptional activity of all cells, including innate and adaptive immune cells.

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