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Getting the immune system to pay attention to cancer

27 November 2013

Research at the Malaghan Institute of Medical Research has revealed a new way of unleashing the cancer-fighting powers of the immune system. It comes in the form of a mixture of live bacteria and urate crystals that are injected into the vicinity of a growing tumour.  The treatment might sound extreme, but the results are hard to ignore.

Our immune system works hard to protect us from the myriad of infectious organisms we are exposed to every day.  Cancer isn’t infectious but could be considered just as deadly as a disease-causing virus.  So why does the immune system appear to largely ignore it?

“The immune system can detect and destroy growing tumours,” says Professor Franca Ronchese, Head of the Malaghan Institute’s Immune Cell Biology Programme.  “Often however, these efforts are thwarted by the tumour’s ability to trick the body into thinking it is normal healthy tissue. Tumours are also very effective at shutting down immune responses. What we are trying to do is to find ways to break through these protective shields.”

One of the key requirements for an effective immune response against a growing tumour is the activation of a specialised class of immune cells called dendritic cells.  The presence of activated dendritic cells inside tumours correlates with better patient survival.  Conversely, impaired dendritic cell function is linked to cancer progression.

“We can detect dendritic cells in the tumours of patients, but their function is often limited,” says Professor Ronchese.  “We wanted to find out whether we could make a cost-effective treatment that activates the dendritic cells present inside these tumours, as this would be a simple therapy to use, even in small hospitals.”

In an attempt to ‘kick start’ the tumour-bound dendritic cells into action, Professor Ronchese and Dr Sabine Kuhn, in collaboration with Drs Jacquie Harper and Joanna Kirman, injected around tumours with compounds known to stimulate an immune response.  These included live bacteria, bacterial products, viral products and even the monosodium urate crystals (MSU) that cause painful inflammation in gout.  Their findings have been published in the international Journal of Immunology.

Out of all the compounds tested, one particular combination stood out – a mixture of MSU and Mycobacterium smegmatis (M. smeg), a non-infectious relative of the bacteria that cause tuberculosis.

The use of live bacteria to treat cancer has been around since the late 1800s.  This followed the remarkable observation at the time by American surgeon Dr William Coley that a particular strep bacterial infection in cancer patients coincided with a shrinking of their tumours. While medical science has progressed considerably since Coley’s original experiments, controlled injection of mycobacteria remains a standard first line therapy for bladder cancer.

“We discovered that the combination of MSU and M. smeg, enhanced anti-tumour immune responses and delayed tumour growth in our experimental breast cancer and melanoma models,” says Professor Ronchese.

"To our knowledge this is the first report that local administration of MSU and M. smeg is an effective form of tumour immunotherapy.  The reasons why both were required for the tumour-specific immune responses we observed are unknown.”

“However, we postulate that combining current cancer treatments such as chemotherapy and radiotherapy, with immune activating treatments such as those described here, will increase the likelihood of complete remission for many different cancers.”

This research was supported by research grants from the New Zealand Cancer Society, New Zealand Lottery Health and the Wellington Medical Research Foundation.

Publication details:

Kuhn S, Hyde EJ, Yang J, Rich FJ, Harper JL, Kirman JR, Ronchese F (2013) Increased numbers of monocyte-derived dendritic cells during successful tumor immunotherapy with immune-activating agents.  J Immunol, 191:1984-92

Image caption: Professor Franca Ronchese and Dr Sabine Kuhn.