STATing the importance of immune modulation by platinum chemotherapeutics
Stanleyson V Hato, I Jolanda M de Vries, W Joost Lesterhuis, Stanleyson V Hato, I Jolanda M de Vries, W Joost Lesterhuis
Abstract
Platinum-based anticancer drugs enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capacity of tumor cells. This immunomodulatory ability is based on the inhibition of STAT6-mediated expression of co-inhibitory molecule PD-L2 and opens up the possibility of using these drugs in combination with other immunostimulatory compounds.
Figures
Figure 1. Immune modulation by platinum chemotherapeutics. (A) Immunosuppressive tumor microenvironment. IL-4/IL-13 production by tumor cells and immune cells (not shown) leads to STAT6 phosphorylation in DCs and tumor cells. STAT6 phosphoylation leads to upregulation of PD-L2 expression resulting in immune evasion by induction of T cell tolerance and anergy. (B) Platinum treated tumor microenvironment. Platinum chemotherapeutics have a direct cytotoxic effect and inhibit STAT6 phosphorylation leading to a downregulation of PD-L2 expression. Decreased PD-L2 expression leads to increased activation and proliferation of T cells by DCs and enhanced recognition of tumor cells by T cells.
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Source: PubMed