Analysis of Circulating Immune Subsets in Primary Colorectal Cancer

SIMPLE SUMMARY: The immune system has a vital role in shaping the development and progression of CRC. Circulating immune subsets are the primary resources of tumor-infiltrating immune cells that could directly count against the tumor. The status of the systemic immunity in CRC patients is still unclear. Our study aims to comprehensively evaluate the circulating immune subsets and gene expression profiles of CRC patients. Here, we show that CRC patients have a more prominent systemic immune suppression than healthy controls, as well as NR3C2, CAMK4, and TRAT1, that might involve regulating the number of circulating T helper cells in CRC patients. The distribution of circulating immune subsets in CRC could complement the regional immune status of the tumor microenvironment and contribute to the discovery of immune-related biomarkers, for the diagnosis of CRC. ABSTRACT: The development and progression of colorectal cancer (CRC) are known to be affected by the interplay between tumor and immune cells. However, the impact of CRC cells on the systemic immunity has yet to be elucidated. We aimed to comprehensively evaluate the circulating immune subsets and transcriptional profiles of CRC patients. In contrast to healthy controls (HCs), CRC patients had a lower percentage of B and T lymphocytes, T helper (Th) cells, non-classical monocytes, dendritic cells, and a higher proportion of polymorphonuclear myeloid-derived suppressor cells, as well as a reduced expression of CD69 on NK cells. Therefore, CRC patients exhibit a more evident systemic immune suppression than HCs. A diagnostic model integrating seven immune subsets was constructed to distinguish CRC patients from HCs with an AUC of 1.000. Moreover, NR3C2, CAMK4, and TRAT1 were identified as candidate genes regulating the number of Th cells in CRC patients. The altered composition of circulating immune cells in CRC could complement the regional immune status of the tumor microenvironment and contribute to the discovery of immune-related biomarkers for the diagnosis of CRC.