β-Lapachone-induced high mobility group box 1 (HMGB1) release activates the host TLR4/MyD88/type I interferon pathway and Batf3 dendritic cell-dependent cross-priming to bridge innate and adaptive immune responses against the tumor.
Our findings identify the importance of tumor cell oncogene activity in modulating the Batf3-dependent DC lineage and reveal therapeutic limitations for combined checkpoint blockade and tyrosine kinase inhibition.
Intratumoral BATF3-dependent DCs are critical determinants for T cell antitumor immunity, effector T cell trafficking to the tumor site, and response to immunotherapies.
Here, we show in several tumor models that although the growth of primary tumors in Batf3-deficient mice, which lack cross-presenting DCs, was not different from primary tumors in wild-type (WT) control mice, Batf3-deficient mice had increased experimental and spontaneous metastasis and poorer survival.