During tumor development and in cancer therapy, extracellular HMGB1 can not only contribute to tumorigenesis but also can stimulate anti-tumor immune responses thought binding to various receptors on different types of cells, such as receptor for advanced glycation end products (RAGE), toll-like receptors (TLRs), chemokine (C–X–C motif) receptor 4 (CXCR4), and T cell immunoglobulin mucin 3 (TIM3) [12–15]. The gene discussed is HMGB1; the disease is neoplasm.