Schwann cells are known to protect and repair neurons. Until now, it was not known that they themselves take over the functions of certain immune cells during nerve healing. For example, they produce signaling molecules that can activate other immune cells. However, it is particularly capable of stopping inflammatory reactions in order to prevent excessive tissue damage and to allow the nerve to regenerate.
“This is necessary, because inflammation releases free radicals that nerve fibers cannot protect themselves against. Therefore, inflammation must be cleared quickly, which is exactly what Schwann cells do,” explains Dr. Sabine Tachner Mandel, who designed the study and co-leaders. Research group at St. Anna CCRI. The new findings, in which the Medical University of Vienna is highly involved, have been published in the journal boiling.
Do Schwann cells protect against malignancy?
How do these findings relate to tumor growth? After a nerve injury, Schwann cells adopt the “repair” mode also found in benign neuroblastomas in children. There, it causes cancer cells to mature and thus reach a stage where they lose their aggressive properties and no longer divide unchecked (Weiss T., Taschner-Mandl S., et al., nat common 2021).
“Based on the current findings, we now suspect that the immune cell functions of Schwann cells also become effective in childhood neuroblastomas. This is because in cancer, there is always some kind of inflammation that never stops. Neuroblastomas, ganglion tumors, and the chronic inflammation associated with them can be stopped by T cells Schwann cells are similar to nerve healing, because unlike malignant tumors, benign neuroblastomas have many Schwann cells in their microenvironment. We also see that a lot of immune cells migrate into these tumors, for which Schwann cells could also be responsible,” she says. Sabine Tachner Mandel.
Healthy Inflammation: Activate it first, then shut it down
In particular, the current study shows that Schwann cells can affect certain immune cells, called T cells, which play an important role in defense against cancer. Schwann cells—both those in nerve regeneration and those in benign tumors—carry MHC-I and MHC-II molecules on their surface that are important for T-cell regulation. Through these molecules, Schwann cells present the features of recognizing substances they have previously taken from their environment.
We have mimicked the inflammatory response in vitro and discovered a whole host of additional stimulatory and inhibitory surface molecules also essential for T-cell activation,” explains Jakob Berner, co-first author of the study and interim doctoral student in the Can Boztog group at St. Anna CCRI. Xuan is able to take in large amounts of substances by phagocytosis.”
As the first nerve-severing immune response, Schwann cells secrete substances that attract T cells, macrophages, and other immune cells. It now turns out that not only an interaction between conventional immune cells occurs, but also between Schwann cells and T cells.
While Schwann cells initially fuel the inflammatory response by releasing interferon-gamma, they can later turn it off by upregulating the T-cell inhibitory molecule PD-L1.
“Activate first, then turn off — that’s the normal process of the inflammatory response. If this is also the case in cancer, it can limit cancer growth,” comments Sabine Tachner-Mandel. Research is now being conducted into whether and how these findings can be used in potential cancer treatments.