The activating effects of TEVs were reversed by treatment of vesicles with proteases and by pre-treatment of neutrophils with an HMGB1 antagonist, TLR4 inhibitors (but not TLR2 and RAGE inhibitors), and HMGB1 knockdown in tumor cells, suggesting the participation of the HMGB1/TLR4 axis in the observed effects of gastric cancer TEVs on neutrophils [228]. The gene discussed is TLR4; the disease is neoplasm.