Disrupted immune cell navigation in lymph nodes of breast cancer patients
14 January 2021
In breast cancer, tumours of different types have divergent effects on the functioning of the lymph nodes. In patients with invasive breast cancer, the blood vessels and supporting tissue of the lymph nodes change, but this does not occur in patients with a non-invasive form of breast cancer (ductal carcinoma in situ). This is shown in a new study from Uppsala University, now published online in the scientific journal Cancers.
In invasive breast cancer, i.e. breast cancer that spreads beyond the original tissue where it arose, cancer cells commonly spread to the lymph nodes (metastasis). Lymph node metastasis indicates an unfavourable prognosis for the patient.
The study now shows that in patients with invasive breast cancer, changes are seen both in the specialised blood vessels of the lymph nodes (high endothelial venules, HEVs) and in the supporting cells that surround these vessels (fibroblastic reticular cells, FRCs). These changes occur even before the cancer cells spread to the lymph nodes (pre-metastatic).
The T cells ability to navigate is impaired
To enable the body to defend itself against the cancer, the T cells – white blood cells that fight diseases – must be able to reach the lymph nodes. They do so through the HEVs assisted by the supporting FRCs. In simple terms, the HEVs may be said to form the roads while the FRCs, surrounding them, serve as road signs, showing the T cells the right way.
“We can identify changes of the T cells indicating that, in invasive breast cancer, their ability to navigate is impaired. But we still want to learn more about the immunological consequences of the changes we see in the HEVs and surrounding FRCs,” says Tove Bekkhus, a PhD student at Uppsala University’s Department of Immunology, Genetics and Pathology, and the first author of the study.
Previous studies have indicated that tumour diseases can affect the functioning of the lymph node vessels, and also their surrounding supporting cells. However, in the present study the two changes were found to be connected, for the first time.
The study is also the first to show that patients who have the non-invasive form of breast cancer lack or have very limited changes of the HEVs in the lymph nodes.
Affects our immune system at several different levels
In patients with invasive breast cancer, on the other hand, such changes are evident even before cancer cells spread to the lymph nodes. This is a new piece of knowledge for understanding why metastasis to the lymph nodes is so common in this type of breast cancer.
“This is a step on the way to understanding better how invasive cancer affects our immune system at several different levels. The lymph nodes are small organs that serve as our body’s defence headquarters. In the lymph nodes, the immune cells get instructions on how to combat the cancer. The fact that cancer cells can spread to the lymph nodes suggests that they must be able to inhibit the immune system there. We now have new opportunities to understand why. Our work also paves the way for evaluating these and other changes in lymph nodes as biomarkers in breast cancer and other tumour types”, says Maria Ulvmar, group leader at the Department of Immunology, Genetics and Pathology at Uppsala University.
Bekkhus et al., Remodeling of the lymph node high endothelial venules reflects tumor invasiveness in breast cancer and is associated with dysregulation of perivascular stromal cells, Cancers 2021, 13(2), 211; https://doi.org/10.3390/cancers13020211
Explanation of the image
The image shows the specialized blood vessels called high endothelial venules (HEVs) (purple) that are required for T cells to find their way into the lymph node. The red arrow shows a HEV vessel with a changed shape, which can no longer function as a pathway for the T cells. The white arrow shows some vessels that are still in normal shape. In green you see the chemokine, CCL21, which together with the vessels is important for the T cells to be able to find the right way.