Immunophenotypic changes in peripheral blood of colorectal cancer patients: a potential diagnostic marker for CD4+ monocytes

Abstract

Colorectal cancer (CRC) can induce stresses on the immune system that can affect both the numbers and function of these cells and the ability of the tumours to evade immune-surveillance. Changes in immune functions can also occur during ageing and these may affect both the ability to fight infections and to protect against cancers. As the incidence of CRC is age-related, the aim of this work was to identify changes in immune cell subtypes that are specific to CRC and not merely due to age-related changes. The immunophenotypes of peripheral blood lymphocytes and monocytes of CRC patients and age-matched healthy controls (HC) were analysed using flow cytometry and surface marker staining. Compared to HC, a lower L:M ratio was observed starting from the early stages of CRC, while numbers of B lymphocytes were lower and CD4+ monocytes were higher in CRC patients. In most patients with CRC, the numbers of helper T cells were lower, while cytotoxic T cells and NK T cells together with CD4+ NKT and CD8+ NKT cells were higher: classical monocytes were lower while intermediate monocytes were higher throughout the stages of CRC, and HLA-DRlowmonocytes were also higher. NKbrightcells were higher while NKdimcells were lower in patients with large tumours. Most of the increased numbers of T cells and monocytes in CRC relate to immunosuppressive phenotypes that may aid tumour evasion. The increase in CD4+ monocytes is likely related to increased numbers of intermediate monocytes, and a threshold of 11.6% CD4+ monocytes can be used as diagnostic marker for CRC with a 60% sensitivity and 88% specificity.