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.

Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.