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Secrets of killer T cells pave the way to improved cancer treatments

March 23, 2016

Researchers have uncovered how the body mobilises killer immune cells in response to infections or cancer cells. This discovery could be harnessed to improve the treatment of chronic infections or cancer, especially cancer immunotherapy.

Dr Axel Kallies, Dr Annie Xin and Dr Frederick Masson at Walter and Eliza Hall Institute (WEHI) in Melbourne investigated how killer T cells are generated during immune responses. Their discovery of how two pathways cooperate to unleash cytotoxic or ‘killer’ T cells was published in this month’s edition of Nature Immunology.

Killer T cells work continuously to detect, attack and kill abnormal cells in our body, for example cells that are infected with viruses or have undergone cancerous changes. The formation of killer T cells is guided by signals, called cytokines, released by other immune cells, said Dr Kallies.

“These signals are transmitted to two separate regulator proteins within the T cell, called Blimp-1 and T-bet,” Dr Kallies said.

“For several years it has been known that these molecules both contribute to the formation of killer T cells, but we haven’t understood how they work together.”

“We showed that the combination of both signals triggers the formation of killer cells that can fight a viral infection. If one of these signals is lost, the immune response is dampened but still functional. This creates a buffered system that helps the organism to fight different types of infections or cancerous cells.”

“It’s a great example of how our body has checks and balances in place to ensure the immune system is switched on at the right time – such as during an infection – but can be toned down at other times to avoid a damaging attack on healthy cells.”

Groundwork for immunotherapy improvement

Dr Kallies said he hopes his research revealing how killer T cells are formed would lay the groundwork for future advances in cancer immunotherapy. CD8 killer T cells have been essential to the recent breakthroughs.

“There have been amazing improvements in immunotherapy recently that can be traced directly back to basic immunology research conducted over the last decade,” he said.

“Our team is now looking at how we can apply our discoveries to approaches aimed at improving cancer therapies.”

The research was supported by the National Health and Medical Research Council, the Australian Research Council, the Sylvia and Charles Viertel Foundation, the US National Institutes of Health, Howard Hughes Medical Institute, and the Victorian Government Operational Infrastructure Support Scheme.

The Australian Cancer Research Foundation has supported WEHI by providing three grants, totalling AUD 5.5million towards cutting edge cancer research equipment and technology.

The original article was published on the WEHI website. Image of Dr Kallies courtesy of WEHI.

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