Double enhancement of immunogenic cell death and antigen presentation for cancer immunotherapy

Immunogenic cell death (ICD) of tumor cells can produce plentiful tumor-associated antigens (TAAs) and release damage-associated molecules to communicate a danger situation. Damage-associated molecular patterns induce the antigen presentation ability of dendritic cells (DCs), activating the immune response cells and generating anti-tumor immune response. However, the immunosuppressive microenvironment in tumor tissues leads to a small amount of DCs in tumor tissues and suppresses their function, limiting the activation of immune response. Herein we report a tumor immunotherapy strategy by the combination of intravenous injection of doxorubicin (DOX)-loaded PLGA nanoparticles (DOX@P) coating with cell membranes (DOX@PM) and intratumoral injection of the lymphotactin (XCL-1)-loaded sodium alginate. The biomimetic nanocarriers facilitate the DOX targeted delivery to tumor, inducing a high degree of ICD. XCL-1 chemokines released from the in situ formed alginate hydrogel recruit a large amount of XCR-1⁺ DCs into the tumor tissue, which can capture more TAAs and mediate more cross-presentation of antigens to activate CD4⁺ and CD8⁺ T cells. As a result, in vivo antitumor experiments indicate that the double enhancement of immunogenic cell death and antigen presentation with this immunotherapy strategy improve the tumor therapy efficacy. This work provides a new strategy for enhanced tumor immunotherapy.