Bacteria to fight cancer

C&I Issue 4, 2023

Read time: 2-3 mins

Maria Burke

Introducing bacteria into the cells of tumours triggers the immune system’s primary responder cells to attack rather than protect a tumour, according to Australian researchers.

The first-responder cells, called neutrophils, are white blood cells that play an important role in defence against infection. While they generally protect against disease, they can also sometimes promote tumour growth. High levels of neutrophils in the blood are usually associated with poorer outcomes in cancer.

‘Using the immune system to fight cancer has been one of the biggest breakthroughs in cancer therapy, but currently immunotherapy for improving T cell [a type of white blood cell that responds to infections] function doesn’t work for all types of cancer,’ says team leader Tatyana Chtanova from the Garvan Institute of Medical Research in Sydney. ‘We decided to use a different type of immunotherapy that targets neutrophils. Since attacking bacteria is the reason for neutrophils’ existence, we had a good inkling that introducing bacteria would bring neutrophils to the site and activate them. We discovered that it’s very effective in getting them to kill the tumours, chewing up their matrix.’

The researchers injected inactivated Staphylococcus aureus microbes into a range of animal cancer models, including Lewis lung carcinoma, triple-negative breast cancer, melanoma and pancreatic cancer. They used intravital imaging – where an imaging window is implanted into the animal tissue – to see inside the tumours in real time.

Before injection, the solid tumours were chronically inflamed, an environment similar to a healing wound. Neutrophils in the tumour were producing a signal protein that stimulates the formation of blood vessels. But after injection of the bacteria, the researchers observed ‘rapid and dramatic’ changes, the most striking of which was a substantial increase in the presence of activated neutrophils (Cancer Res.; doi: 10.1158/0008-5472.CAN-21-4025). These neutrophils were highly mobile and formed clusters in the tumour which then remodelled tumour tissue and repressed its growth.

The study also shows that the neutrophils change at the gene expression level: they begin to secrete molecules that will attract fighter T cells as reinforcement. The team hopes their work will lead ultimately to better treatments for patients with advanced or previously untreatable cancers. Over the next three to five years, they will develop the therapy to fight metastasis, the spread of cancer to other areas of the body, with clinical trials to follow.

Header image: Cancer cells (green) being attacked by neutrophils (red) in the collagen structure (blue) of a tumour’s microenvironment
Jacqueline Bailey/Dr Chtanova’s Innate Tumour Immunology Lab at Garvan