Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy.

Automated summary

Tumor microparticles (T-MPs) are potential candidates for tumor vaccines, but the mechanism of how they stimulate anti-tumor immune response is not fully understood. This study demonstrates that T-MPs induce macrophages to release CCL2, attracting monocytes to the vaccine injection site and enhancing antigen endocytosis. The monocytes then differentiate into moDCs, presenting tumor antigens to T lymphocytes and promoting a strong anti-tumor immune response. Furthermore, T-MPs activate cGAS-STING signaling, upregulate IRF4 expression in monocytes, and confer the ability to treat tumors. This research provides insights into the development of novel vaccination strategies and the clinical application of T-MPs in oncotherapy.