Immune Checkpoint Inhibitors in Cancer Therapy—How to Overcome Drug Resistance?

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) are an important strategy in cancer therapy. However, with the widespread clinical use of ICIs, people gradually found that ICIs may not be effective enough to eliminate tumor tissue for certain patients. The resistance to ICI treatment makes some patients unable to benefit from their antitumor effects. Therefore, it is vital to understand their antitumor and drug resistance mechanisms to better narrow the ICI-resistant patient population. This review outlines the antitumor action sites and mechanisms of different types of ICIs and lists the main reason of ICI resistance based on recent studies. Finally, we propose current and future solutions for resistance to ICIs. ABSTRACT: Immune checkpoint inhibitors (ICIs), antagonists used to remove tumor suppression of immune cells, have been widely used in clinical settings. Their high antitumor effect makes them crucial for treating cancer after surgery, radiotherapy, chemotherapy, and targeted therapy. However, with the advent of ICIs and their use by a large number of patients, more clinical data have gradually shown that some cancer patients still have resistance to ICI treatment, which makes some patients unable to benefit from their antitumor effect. Therefore, it is vital to understand their antitumor and drug resistance mechanisms. In this review, we focused on the antitumor action sites and mechanisms of different types of ICIs. We then listed the main possible mechanisms of ICI resistance based on recent studies. Finally, we proposed current and future solutions for the resistance of ICIs, providing theoretical support for improving their clinical antitumor effect.