Effect of the HDAC inhibitor SAHA on the immunomodulatory properties of MSC and tumor stroma cells

Abstract

Histone deacetylase inhibitors, like suberoylanilide hydroxamic acid (SAHA), are potential new drugs in oncologic treatment protocols. They can impact on proliferation and function of T cells. We analysed the effects SAHA on T cells directly as well as on mesenchymal stromal cells (MSC), which are known to modulate T cell responses. SAHA reduced the suppressive effects of MSC on PBMC. In previous studies we found that tumor stromal cells (TStrC) impair T cell function. As TStrC share several properties with MSC, we hypothesized that in this particular setting SAHA may facilitate tumorimmunological responses by downregulation of the immune suppression by TStrC. We isolated TStrC from neuroblastoma patients and analysed the effect of SAHA on these TStrC including cytokine patterns. Proliferation TStrC was only slightly affected at the pharmacologically relevant concentration of 1,2µM. After treatment with SAHA, TStrC showed reduced inhibition of the proliferation of PBMC and cytotoxicity of NK cells. These findings suggest, that SAHA may modify the tumor microenvironment to allow for more efficient anti-tumor immune responses.