Disrupted immune cell navigation in lymph nodes of breast cancer patients

2021-01-12

Different types of breast cancer tumours differ in how they affect the function of the lymph nodes. In patients with invasive breast cancer, the vessels and supporting tissue of the lymph nodes are altered, which cannot be seen in patients with a non-invasive cancer called (ductal cancer in situ). This is shown in a new study from Maria Ulvmar’s group at IGP, published online in the scientific journal Cancers.

In patients with invasive breast cancer, i.e. cancer that spreads outside of the original cancer tissue, it is common that it spreads (metastasises) to the lymph nodes. This spread indicates a worse prognosis for the patient. The new study now shows that in patients with invasive breast cancer, changes are seen in the lymph nodes’ specialised blood vessels, the high endothelial venules (HEVs), and in the supporting that surround the vessels cells (fibroblastic reticular cells, FRCs). This occurs already before the cancer cells are spread to the lymph nodes.

To enable the body to defend itself against the cancer, T cells, – white blood cells that fight diseases – have to reach the lymph nodes. They do so through the HEV vessels, assisted by the supporting FRCs. In  simple terms, the HEVs may be said to form the roads, and the supporting FRCs serve as the road-signs, that allow the T cells to find their way.

“We have found changes in the T cells that indicate that their ability to navigate is impaired in patients with invasive breast cancer. However, we still need to learn more about the immunological consequences of the changes that we see in the HEVs and surrounding stromal cells,” says Tove Bekkhus, PhD student in Maria Ulvmar’s group and first author of the study.

Even if it is previously known that both the lymph node vessels, e.g. their shape, and the surrounding stromal cells change during the cancer disease, this is the first study where the changes could be linked to each other. The study also shows for the first time that patients with non-invasive cancer do not have these changes in the lymph nodes.

In patients with invasive breast cancer, the vessel changes were present already before the cancer had spread to the lymph node. This is important knowledge for understanding why lymph node metastasis is so common in this type of breast cancer.

“This is a step towards a better understanding of how invasive cancer influences our immune response at many different levels. The lymph nodes are small organs that act as the defence headquarters of our body, but to which the cancer cells spread very early in invasive cancer. In the lymph nodes, the immune cells are instructed on how to fight infections and cancer. The spread of cancer cells to the lymph nodes indicates that they must be able to inhibit the immune defence there. We now have new possibilities to understand why,” says Maria Ulvmar, who has led the study.

Microscope image showing altered and nprmal blood vessels in a lymph node
The image shows the s specialised blood vessels called high endothelial venules (HEVs) (purple) that are needed for the T cells to find their way into the lymph node. The red arrow indicates HEV vessels with an altered shape that no longer function as a route for the T cells. The white arrow indicates vessels that are still normal. The green colour indicates staining of a substance that together with the vessels is important for the T cells to find the right way.

More information:
Article in the journal Cancers
Maria Ulvmar’s research