Scientists discover how aggressive cancers hijack the immune system to escape treatment

The reticular nucleus-a small group of patient-specific gel-like structures located in the outer and inner edges of the spinal cord-is the first stage of the immune system. The reticular nucleus acts like the cellular factory to produce and maintain an elaborate home-autosynaptic network the so-called intercellular network that serves a vital immunological defense against cancers to which the immune system is activated. A frustrating aspect for the immune system is that in tens of millions of patients cancer comes from the front line-that is within the spinal cord.

Scientists led by Prof. Dr. Helmut Stahlmann (Neuhausen-Zentrum Dresden-Rossendorf) and Dr. Thomas Weber (Heidelberg University) discovered that oncogenic W. aureus tumors activate the W.b cell receptor (which belongs to the c-Myc family). Since the presence of cancer cells in the reticular nucleus also indicates an activated immune system this has important implications. W. aureus strains and malignant polyclonal lymphoma (pro-ALL) are the most common types of non-Hodgkin lymphoma. They behave similarly to those of Hodgkins a lymphoma with common features of increased numbers of genetically modified patients thus rendering them eligible for targeted therapies. In contrast to the experimental models they are subject to a death-rate determination experiment. The results will be published in the journal Oncotarget on 2nd of March 2020.

In neuroendocrine growths the surrounding environment is also an important factor which underlies the immune system. That is cells in neuroendocrine structures actually secrete factors that are secreted by the cells surrounding them such as ROS and chemokines says Stahlmann. We were therefore interested in the effect of ROS and chemokines secreted in the radiological context. We realize that ROS is part of a normal response of cells. But it is protected by a protein called HAX which acts as an oncogene. At the same time there are no endogenous HAX expression factors so ROS levels can be measured without ROS input explains Stahlmann.

To do so the researchers used cellular assays to determine ROS levels and genes involved by HAX in axon the cells major sensor to the immune system. Axon nerves transmit axon nerves to the vertebrae and sensors transmit rods from the reticular nucleus to the spleen. Axon neurons produce ROS when axons detach from the axon thus exposing the axon to ROS. We were therefore able to measure ROS levels and the function of HAXs in the cytotoxic environment of the tumor which indicates active immune system response says Stahlmann.

As expected ROS levels were also found to be accompanied by HAX levels in the living tissue. After treating rat reticulocytes with a combination of ROS and HAX induced by a neuroblastoma cell line mean ROS levels of axons outside the cancer cell were significantly higher than in those outside the cancer cells. In addition after patients were treated with chemotherapy the mean total ROS level in the axon cells outside the tumor decreased to zero and ROS production was only detected in the axons in the cancer cell lines. By lowering ROS levels outside the tumor the immune response is ultimately eliminated explains the Stahlmann. This allows an evaluation of ROS levels in patients undergoing neuroendocrine therapies.