Histone deacetylase inhibitors prevent activation of tumour-reactive NK cells and T cells but do not interfere with their cytolytic effector functions.

Histone deacetylase inhibitors (HDIs) exert direct tumour-toxic activity and sensitise tumour cells for other therapeutic regimens as well as the cytotoxic effects of activated immune cells. However, the HDI suberoylanilide hydroxamic acid (SAHA; vorinostat) interfered with the IL-2 activation of human NK cells and the priming of human tumour-specific T cells. In contrast, NK or T cells which were activated in the absence of HDIs became resistant to their immunosuppressive action. Therefore, as a therapeutic strategy, first the patient's immune system might be stimulated and then HDIs could sensitise the tumours for the attack of the pre-activated immune effector cells.