Whether tumours develop and spread is dependent, amongst other things, on the body’s ability to defend itself against them. Scientists from the University Women’s Hospital and the German Cancer Research Centre in Heidelberg have identified two signalling molecules in breast cancers that play a key role in activating defence cells against tumours. The scientists also found that patient prognosis improves when activated defence cells are present. The results have recently been published in the journal “Cancer Research”.
It has been known for quite some time that it is possible in principle for the body to have an immune response to tumour cells and that this response might also have a positive effect on the progression of breast and colon cancer. In the test tube, certain immune cells (T-cells) that specifically target these tumours have been shown to completely destroy tumour cells. However, no information is currently available on what the body needs to be able to produce active tumour-specific T-cells, and how this affects the further progression of disease pathogenesis.
Researchers in the teams of Dr. Christoph Domschke, Dr. Florian Schütz (University Women’s Hospital in Heidelberg) and Dr. Philipp Beckhove, head of the “Translational Immunology” work group at the German Cancer Research Centre, have examined 207 breast cancer patients and found that the disease outcome is much better and has a reduced mortality risk when tumour-specific T-cells are present in the patients’ bone marrow. However, the activation of these cells depends on numerous different factors.
The researchers investigated the presence of 27 different cytokines (substances that are secreted by specific immune system cells) and growth factors in breast cancer samples. "We found that the composition of the signalling molecules in the tumours is key for an immune response to occur in the bone marrow," said Dr. Christoph Domschke. Before the bone marrow is able to produce defence cells, dendritic cells have to signal the presence and specific properties of cancer cells in the body. "However, the dendritic cells only induce tumour-reactive T-cells if the tumour tissue has a particular composition of cytokines: high concentrations of interferon alpha (IFNa) and low concentrations of transforming growth factor beta1 (TGFß1) are necessary for an effective immune response to occur," said Domschke.
"Our results provide evidence that a functional immune response is key for the prognoses of breast cancers," explains the coordinator of the cooperative research project, Philipp Beckhove. Therefore, future studies on individualised immunotherapies against breast cancer must take into account the concentration of immunological signalling substances in the tumours.
Intratumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer-Specific Immune Responses and Their Correlation to Prognosis.
Christoph Domschke, Florian Schuetz, Yingzi Ge, Tobias Seibel, Christine Falk, Benedikt Brors, Israel Vlodavsky, Nora Sommerfeldt, Hans-Peter Sinn, Marie-Christine Kühnle, Andreas Schneeweiss, Alexander Scharf, Christof Sohn, Volker Schirrmacher, Gerhard Moldenhauer, Frank Momburg, Philipp Beckhove, Cancer Research 2009; 69(21): 8420-8428.