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

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.