The Host-Defense-Peptide-Mimicking Synthetic Polypeptides Effectively Enhance Antitumor Immunity through Promoting Immunogenic Tumor Cell Death.

Cancer immunotherapy is to artificially stimulate the immune system against tumor cells. Effectively increasing the immunogenicity of dying tumor cells has great potential to stimulate the anticancer immune responses. Recently, a synthetic cationic anticancer polypeptide (ACPP) is prepared, which mimics the host defense peptides, to effectively inhibit tumor growth by directly inducing rapid necrosis of cancer cells through a membrane-lytic mechanism. Thus, this ACPP has the potential ability to induce immunogenic cancer cell death (ICD) and promote antitumor immunity. Herein, it is reported that ACPP successfully induces ICD in mouse colon cancer cells, resulting in effectively promoting T-cell-dependent antitumor immune responses by enhanced activation of dendritic cells. Interestingly, the level of natural killer cells, which are another kind of antitumor effector cell, in tumor microenvironment is also significantly increased by ACPP. The ratio of M1/M2 tumor-associated macrophages is further obviously increased, indicating that tumor immunosuppressive microenvironment has been effectively reprogramed. More importantly, it is found that the anticancer immunity induced by ACPP is dose dependent. Finally, 40% of the established CT26 tumors are completely eliminated by ACPP treatment with an optimized dose. This study proposes a simple and effective strategy for promoting cancer immunotherapy.