As early as 150 years ago, doctors observed a positive influence of bacterial infections in cancer patients. Despite much progress has been made in the past decades, this therapeutic approach failed to achieve a breakthrough. It remained unclear how the bacteria act against the tumour and what role the immune system plays in this complex process. Researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig recently shed some light on these issues. They published their results in the International Journal of Cancer.
A number of bacteria has been tested as anti-cancer agents in recent years. This was a balancing act since some of the most-promising candidates are harmful pathogens as well. For example Salmonellae have a pronounced anti-tumour activity, but can also cause sepsis. "The perfect bacterium for the treatment of cancer has not been found yet," says Dr Christian Stern, who is a former research scientist of the "Molecular Immunology" department at the HZI and principal author of the study. "Although it has been known for a while that the bacteria are not responsible for tumour rejection without help, the immunological background of tumour control by bacteria was not studied in detail until now."
In this study, the researchers were not so much interested in how the bacteria act against the tumour, but rather in the role of the immune system in this process. "We identified T-cells as a crucial and indispensable cell type for tumour control in mice. We excluded basically all other candidate cells of the immune system," says Dr Siegfried Weiß, whose is the head of the "Molecular Immunology" department. The scientists found that the bacteria play a much lesser role than had been thought. They simply jump-start the body's inherent defence: The infection induces an immune response during which the TNF-alpha messenger substance is released. As a result, blood vessels in the tumour are destroyed and part of the tumour dies off. Moreover, T-cells directed at the tumour, which are present before the infection, but are in a dormant state, are activated. These cells are driven by the bacteria to specifically attack the remaining tumour and might even resolve it completely.
"As a result, healed mice develop a specific immunity to the tumour cells. If the same tumour develops again, for instance by in the form of metastases, these should be rejected as well," says Stern. In addition to the cytotoxic T-cells, which are specialised on killing infected or abnormal cells, the so-called T-helper cells were also able to destroy tumours by themselves. Usually, this type of T-cells only serves a mediating role and does not actively attack these kind of cells.
"We just demonstrated, in more detail and for the first time, the contribution the immune system has in bacteria-mediated tumour therapy and showed that an effective immunological memory is formed," says Weiß. Understanding these processes better can help improve the therapy and gets the researchers one step closer to their goal to use this therapy in humans in the future.
Original publication:
Christian Stern, Nadine Kasnitz, Dino Kocijancic, Stephanie Trittel, Peggy Riese, Carlos A. Guzman, Sara Leschner, Siegfried Weiss. Induction of CD4+ and CD8+ anti-tumor effector T cell responses by bacteria mediated tumor therapy. Int J Cancer 2015, DOI: 10.1002/ijc.29567.
