Editing cancer with the immune system

Mark Smyth

Immunologists have long suspected that the immune system plays an important and intricate role in combating cancer.

Hypotheses about immune cells patrolling the body to keep cancer at bay were proposed decades ago to explain events such as tumours that suddenly stop growing or even go away, undetected dormant tumours transferred to organ recipients following a transplant, and immune-depleted subjects being more susceptible to cancer.

However, hard laboratory-based evidence for this idea was scant and the idea of cancer ‘immunosurveillance’ remained controversial. In 2001, Professor Robert Schreiber of the Washington University School of Medicine in St Louis and colleagues proposed a new elaboration of the model called ‘cancer immunoediting’.

In this model, three outcomes are possible following a cancerous insult – elimination, equilibrium or escape of the tumour – with all influenced and perhaps modulated by immune function.

It was also around this time that Professor Mark Smyth, who heads the cancer immunology program at the Peter MacCallum Cancer Centre in Melbourne, started to collaborate with Schrieber on some mouse models.

The ultimate application of their research was targeted at developing a way to tweak the immune system in favour of elimination or at least equilibrium, while preventing escape of the tumour to grow out and fulfil its malignant potential.

At the 2008 Australasian Society for Immunology (ASI) meeting in Canberra this week, Smyth will present his team’s latest results on the research, published in Nature late last year. He will also present new data from a different model that validates their primary findings.

Smyth’s interest in this area grew out of earlier work he was doing with Professor Joe Trapani at Peter Mac on cytotoxic lymphocyte mechanisms to protect against viral infections.

“I have always been very interested in investigating basic biological responses using mice, so I started to analyse some of the knockouts we had procured for the cell-death/apoptosis research for the importance of these same pathways in tumour development,” Smyth says.

“The basic idea is that the immune system has an ongoing relationship with tumours as they develop and is part of the extrinsic regulation of tumour growth and spread.

“Most of us are familiar with the gatekeepers of the genome like the p53 gene and other tumour suppressors, as well as defined oncogenic changes that can occur. These are all genetic fundamentals that underlie cancer development and they are all intrinsic to the cancer cell.

“But then there are all these other processes that determine whether a lesion becomes clinically evident, and the immune system is one of those, and we have now spent a lot of time trying to define this role in mouse models.”

Immune pathways had been looked at previously in terms of infection, Smyth says, but not to any great depth in relation to tumour control, and certainly not in longitudinal models. “We thought that these earlier systems were not very representative of what really happens in cancer,” he says.

• Share
  Share this article

  •  google+
  • facebookfacebook
  • slashdotslashdot
  • diggdigg
  • RedditReddit
  • stumbleuponstumbleupon
  • linkedinlinkedin
  • twittertwitter
• print
• email
• Bookmark