Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer.

OBJECTIVE:Liver cancer is a deadly malignancy associated with high mortality and morbidity. Less than 20% of patients with advanced liver cancer respond to a single anti-PD-1 treatment. The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade (ICB). However, the underlying mechanism remains largely unknown. METHODS:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes MycKrasG12D-/-ex vivo+RESULTS:Orthotropic pTMK/Trp53 -/-+++CONCLUSIONS:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB, and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.