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Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
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p38 MAPK-inhibited dendritic cells induce superior antitumour immune responses and overcome regulatory

Yong Lu1, Mingjun Zhang1, Siqing Wang2

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Nature Communications
|June 25, 2014
PubMed

Dendritic cell (DC)-based cancer immunotherapy is a promising method, but so far has demonstrated limited clinical benefits. Regulatory T cells (Tregs) represent a major obstacle to cancer immunotherapy approaches. Here we show that inhibiting p38 MAPK during DC differentiation enables DCs to activate tumour-specific effector T cells (Teff), inhibiting the conversion of Treg and compromising Treg inhibitory effects on Teff. Inhibition of p38 MAPK in DCs lowers expression of PPARγ, activating p50 and upregulating OX40L expression in DCs. OX40L/OX40 interactions between DCs and Teff and/or Treg are critical for priming effective and therapeutic antitumour responses. Similarly, p38 MAPK inhibition also augments the T-cell stimulatory capacity of human monocyte-derived DCs in the presence of Treg. These findings contribute to ongoing efforts to improve DC-based immunotherapy in human cancers.

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