Combination Cancer Immunotherapy of Nanoparticle-Based Immunogenic Cell Death Inducers and Immune Checkpoint Inhibitors

Abstract

Cancer immunotherapy is a promising treatment strategy that aims to strengthen immune responses against cancer. However, the low immunogenicity of tumor cells and inhibition of effector T cells in the tumor immunosuppressive microenvironment remain two major challenges. Immunogenic cell death (ICD) inducers not only directly kill cancer cells but also increase the tumor immunogenicity and induce antitumor immune responses. Immune checkpoint inhibitors can alleviate the inhibition of immune cells. Significantly, the combination of ICD inducers and immune checkpoint inhibitors elicits a remarkable antitumor effect. Nanoparticles confer the ability to modulate systemic biodistribution and achieve targeted accumulation of administered therapeutic agents, thereby facilitating the clinical translation of immunotherapies based on ICD inducers in a safe and effective manner. In this review, we summarize the nanoparticle-based chemical and physical cues that induce effective tumor ICD and elicit an antitumor immune response. In particular, combination of ICD inducers with immune checkpoint inhibitors can further reverse immunosuppression and prevent tumor metastasis and recurrence. An overview of the future challenges and prospects is also provided.

Keywords: immune checkpoint inhibitors; immunogenic cell death; nanoparticles; tumor immunotherapy.