Push and release: TLR9 activation plus STAT3 blockade for systemic antitumor immunity

Oncoimmunology. 2014 Jan 1;3(1):e27441. doi: 10.4161/onci.27441. Epub 2014 Jan 3.

Abstract

Proper immunostimulation ("push") and immune checkpoint blockade ("release") are both critical for the efficacy of anticancer immunotherapy. We have recently shown that activating Toll-like receptor 9 (TLR9) while specifically blocking signal transducer and activator of transcription 3 (STAT3) in leukemic cells enhances their immunogenicity, allowing for CD8+ T cell-mediated tumor eradication. These findings underscore the therapeutic potential of such a "Push & Release" strategy against hematological malignancies.

Keywords: STAT3; TLR9; acute myeloid leukemia; cancer immunotherapy; immune checkpoint; immunogenicity; siRNA.