Tumours are known to evade the immune system by a variety of mechanisms, one of which is the recruitment of ‘myeloid-derived suppressor cells’ (MDSC). MDSCs suppress the ability of the immune system’s killer T-cells to destroy cancer cells. It is known that the more MDSCs present, the worse the prognosis or therapy response of the patient. Tumours secrete signal molecules such as interleukin-6 (IL-6) that help in recruiting MDSCs, however; the mechanisms behind IL-6 tumour secretion are quite unknown.
Now, a study from researchers at Karolinska Institutet is the first to suggest that cells in the tumour blood vessels contribute to a local environment that protects the cancer cells from these tumour-killing immune cells. The team state that their study can contribute to the development of better immune-based cancer therapies. The study is published in the Journal of the National Cancer Institute.
Previous studies show that pericytes, which envelope the vascular endothelium throughout the body, are often targeted to promote vascular normalization and restore normal function of blood vessels in cancer treatment. The goals of pericyte-targeted therapy tend to promote proper vascular normalization of the tumour.
Tumour vascular normalization is shown in earlier studies to prevent metastasis, make radiation more effective in killing tumour cells and increase delivery of cancer cell-directed therapies as well as the efficacy of focal therapies such as surgery or radiation. It has also been shown to increase recognition by the host immune system as in an immunotherapy. However, much is still unknown pertaining to pericyte origin, function, or interaction with other tumour components. Emerging evidence suggest that pericytes may regulate leukocyte transmigration.
The current study found that tumour pericytes critically manipulate the tumour environment, helping the cancer cells escape immune surveillance. The lab explain that understanding the interplay between tumour pericytes, malignant cells, and the immune system might help in designing more precise and effective therapeutic approaches.
The results show that the higher the number of pericytes, the more normal the tumour environment looked like. Data findings show that diminished pericyte numbers altered the microenvironment and correlated to higher IL-6 expression from the malignant cells and more MDSCs. The researchers also identified a subset of breast cancer patients who had fewer pericytes and increased MDSCs, correlating to a worse prognosis and more aggressive characteristics of the tumour.
The team surmise that their work suggests that ways to increase the numbers of pericytes could potentially decrease IL-6 expression, which could then improve cytotoxic T-cell activity and result in an antitumour effect.
Source: Karolinska Institutet