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

Abstract

Necroptosis is a form of programmed cell death (PCD) characterized by RIP3 mediated MLKL activation and increased membrane permeability <i>via</i> 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 <i>P. aeruginosa</i> showed its potential to suppress tumor growth and enable long-lasting anti-tumor immunity <i>in vivo</i>. What's more, phosphorylation- RIP3 and MLKL activation induced by <i>P. aeruginosa</i> infection resulted in tumor cell necrotic cell death and HMGB1 production, indicating that <i>P. aeruginosa</i> can cause immunogenic cell death. The necrotic cell death can further drive a robust anti-tumor response <i>via</i> 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 <i>P. aeruginosa</i> can catalyze DC maturation, which enhanced the antigen-presenting ability of DC cells. These findings demonstrate that <i>P. aeruginosa</i> can induce immunogenic cell death and trigger a robust long-lasting anti-tumor response along with reshaping tumor microenvironment.