In the present work, we had set out to investigate two major hypotheses: ➀ Nano-DOX could stimulate tumor cells to release HMGB1 which will act through the RAGE receptor to promote NF-κB-dependent PD-L1 expression in the tumor cells and PD-1 expression in the TAMs; and ➁ blockade of Nano-DOX-induced PDL-1 in the tumor cells by BMS-1 will enhance TAM-mediated anti-tumor immune response stimulated by Nano-DOX, thus achieving therapeutic synergy with Nano-DOX. Here, PDCD1 is linked to neoplasm.