AUTHOR=Qi Jia-long , He Jin-rong , Jin Shu-mei , Yang Xu , Bai Hong-mei , Liu Cun-bao , Ma Yan-bing 

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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.610651

DOI=10.3389/fonc.2020.610651

ISSN=2234-943X

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