Dysregulation of systemic immunity in colorectal cancer and its clinical applications as biomarkers and therapeutics

The immune system plays critical roles in the initiation and progression of colorectal cancer (CRC), and the majority of studies have focused on immune perturbations within the tumor microenvironment. In recent years, systemic immunity, which mainly occurs in the periphery, has attracted much attention. In CRC, both the tumor itself and treatments have extensive effects on systemic immunity, characterized by alterations in circulating cytokines and immune cells. In addition, intact systemic immunity is critical for the efficacy of therapies for CRC, especially immunotherapy. Therefore, various strategies aimed at alleviating the detrimental effects of traditional therapies or directly harnessing the components of systemic immunity for CRC treatment have been developed. However, whether these improvements can translate to survival benefits requires further study. This review aims to comprehensively outline the current knowledge of systemic immunity in CRC.