Mediated Necroptosis in Mouse Tumor Cells Induces Long-Lasting Systemic Antitumor Immunity.

Necroptosis is a form of programmed cell death (PCD) characterized by RIP3 mediated MLKL activation and increased membrane permeability MLKL oligomerization. Tumor cell immunogenic cell death (ICD) has been considered to be essential for the anti-tumor response, which is associated with DC recruitment, activation, and maturation. In this study, we found that showed its potential to suppress tumor growth and enable long-lasting anti-tumor immunity . What's more, phosphorylation- RIP3 and MLKL activation induced by infection resulted in tumor cell necrotic cell death and HMGB1 production, indicating that can cause immunogenic cell death. The necrotic cell death can further drive a robust anti-tumor response promoting tumor cell death, inhibiting tumor cell proliferation, and modulating systemic immune responses and local immune microenvironment in tumor. Moreover, dying tumor cells killed by can catalyze DC maturation, which enhanced the antigen-presenting ability of DC cells. These findings demonstrate that can induce immunogenic cell death and trigger a robust long-lasting anti-tumor response along with reshaping tumor microenvironment.