Role of tumor cell intrinsic factors in colorectal cancer progression and immune landscaping

Abstract

The poor response of most colorectal cancer (CRC) patients to immune checkpoint inhibitors (ICIs) is a major unmet clinical need. The impaired antigen presentation process and immune evasive mechanism underlie the unfavorable responses to ICIs. We demonstrated that low ACKR4 expression in tumors impairs dendritic cell migration and is associated with poor immune infiltration within the tumor microenvironment. Additionally, we identified CEP55 as an immune evasion gene in CRC that is upregulated in multiple cancer types and may contribute to tumorigenesis. Most importantly, these studies showed that low ACKR4 expression and overexpression of CEP55 in CRC cause insensitivity to ICIs. Our findings suggest that ACKR4 and CEP55 can be potential targets to sensitize CRC to ICIs.