Although many of the preclinical studies on HMGB1-mediated neuro-inflammation have focused on the pathogenesis of neurological disorders [166,167], they are also likely to be implicated in establishing an immune microenvironment in the brain that favors immunosuppression and tumor growth, possibly driven by microglia and M2-like macrophages [168,169], exacerbated by HMGB1-activated NET formation by infiltrating neutrophils [170]. This evidence concerns the gene HMGB1 and neoplasm.