**Abstract**

Cancer immunotherapy employing immune checkpoint inhibitors (ICI) has revolutionized the tumor therapy far beyond their impressing clinical effects. Immune checkpoint therapy (ICT), which is directly involved in different immunosuppressive mechanisms at tumor sites, has been thoroughly studied. Nevertheless, the "off-target" effects of ICIs following systemic administration is still challenging. In addition, the clinical response rate of ICT is still unsatisfactory in that only a few patients hold lasting benefits. In this chapter, the mechanism of most widely used ICIs, including those based on CTLA-4 and PD-1/PD-L1, has been introduced. The approaches to enhancing the efficacy of ICT have been highlighted, namely improving targeted delivery of ICI by employing nanotechnology, modulating the immunosuppressive tumor microenvironment (TME), and combining ICT with other therapies. We hope advanced strategies summarized in this chapter would further inspire the development of ICT to boost their effectiveness while minimize unwanted side effects.

**Keywords:** cancer immunotherapy, immune checkpoint, targeted delivery, immunomodulation, combined therapy
