A high infiltration of macrophages in colorectal cancer is associated with improved prognosis for patients, which is the opposite to what is observed in many other cancers. This study aimed to understand the anti-tumour action of macrophages in colorectal cancer.
Multicolour flow cytometry, ELISA and qPCR were used to define a functional phenotype of human macrophage populations in vitro. Corresponding populations were subsequently detected, using flow cytometry, in both tumour tissue and non-transformed bowel tissue from colorectal cancer patients. A significantly greater frequency of inflammatory macrophages (Tumour = 0.99±0.2615, Control bowel = 0.2675±0.1070, mean±SEM, Wilcoxon matched-pairs signed rank test p = 0.0156, n = 7) was observed in the tumour tissue of each patient.
Analysis of patient samples also revealed other populations of myeloid derived immune cells. The frequency of myeloid derived suppressor cells (CD45+CD33+CD11b+CD64-CD14-) was significantly increased (Tumour = 0.6431±0.2215, Control bowel = 0.2554±0.0717, p = 0.0313, n = 7) in tumour tissue compared to control bowel. A large population of gut resident macrophages was observed in both tumour and control bowel tissue. These macrophages have previously been described as highly phagocytic and unresponsive to cytokine stimulation – a phenotype that could be beneficial in restricting tumour growth. Here, this population could be subdivided into gut resident (CD45+CD33+CD14-CD11b-CD64-) and inflammatory gut resident (CD45+CD33+CD14+CD11b+CD64+) macrophages.
Macrophages (CD45+CD64+CD11b+), sorted from both tumour and control bowel tissue, were cultured with T cells (CD3+) sorted from patient blood. Tumour macrophages increased T cell IFN-γ and IL-17 production compared to T cell cultured alone, whereas control bowel macrophages did not.
This study highlights the complexity of macrophages and provides methods to examine them ex vivo from human tissue. Data gained from this study could be used for future investigation of macrophages as both prognostic and therapeutic targets.