Targeting the antigen processing and presentation pathway to overcome resistance to immune checkpoint therapy

Despite the significant clinical advances with the use of immune checkpoint inhibitors (ICIs) in a wide range of cancer patients, response rates to the therapy are variable and do not always result in long-term tumor regression. The development of ICI-resistant disease is one of the pressing issue in clinical oncology, and the identification of new targets and combination therapies is a crucial point to improve response rates and duration. Antigen processing and presentation (APP) pathway is a key element for an efficient response to ICI therapy. Indeed, malignancies that do not express tumor antigens are typically poor infiltrated by T cells and unresponsive to ICIs. Therefore, improving tumor immunogenicity potentially increases the success rate of ICI therapy. In this review, we provide an overview of the key elements of the APP machinery that can be exploited to enhance tumor immunogenicity and increase the efficacy of ICI-based immunotherapy.

Automated summary

This review discusses the significant clinical advances of immune checkpoint inhibitors (ICIs) in cancer patients. However, response rates to ICIs vary and do not always result in long-term tumor regression. Therefore, it is crucial to identify new targets and combination therapies to improve response rates and duration. The antigen processing and presentation (APP) pathway has been shown to be a key element in enhancing tumor immunogenicity and increasing the efficacy of ICI-based immunotherapy.