Sendai virus acts as a nano-booster to excite dendritic cells for enhancing the efficacy of CD47-directed immune checkpoint inhibitors against breast carcinoma

摘要

Dendritic cells (DCs) are vital hubs for exciting systemic adaptive immune responses. But the uppermost antigen presenting cells are in a state of severe suppression in breast carcinoma for making tumor cells more resistant and viable. In order to reverse this immunosuppressive state in the tumor microenvironment, here we showed that non-pathogenic Sendai virus (SeV) is employed to execute multi-channel recruitment and excitation of DCs. Simultaneously, the signal of “don’t eat me” on the surface of tumor cells is blocked with a CD47 blocker to greatly enhance the phagocytosis and antigen presentation of macrophages to the tumor cells. With the excitation of these two cells by SeV and CD47 blocker nanocomposites, breast carcinoma antigens are presented to the lymph nodes in large numbers to mature T lymphocytes for specifically killing tumor cells. Our findings indicate that the nanohybrids can successfully excite DCs and macrophages in vitro and in vivo, and then systemically arouse cytotoxic T lymphocytes and helper T lymphocytes, and further motivate the formation of humoral immunity and immune memory. Therefore, the oncolytic nanocomposite strategy combining non-genetically modified viruses and immune checkpoint inhibitors might serve as the next generation of personalized anti-tumor immunotherapy agents, representing an alternative way to suppress tumor metastasis and recurrence.