Targeting macrophages rescues immune dysfunction in the elderly

WESTERN Australian researchers are bridging the gap in knowledge between the aging process and anti-cancer immune responses.

elderley immune“Immune dysfunction is not permanent and in fact can be restored to function similarly to a young immune system”—Dr Jackaman. Image: Luca

The majority of cancers, particularly mesothelioma and lung cancer, develop in the aging population, where it is well recognised that there is a decline in immune system function.

However, remarkably few studies have been published investigating the association between the age-related decline in immune system function and the development of cancer.

Research from Curtin University and the University of Western Australia published in Aging Cell, addressed this issue by investigating age-related and tumour-related dysfunction by examining a crucial cell of the immune system, the macrophage.

Macrophages are white blood cells involved in innate and adaptive immunity, where they phagocytose (remove) debris and pathogens while stimulating an immune response from other cells of the immune system.

Researchers found targeted immunotherapy of macrophages could improve age-related immune dysfunction.

“Macrophages make up to 50 per cent of the mesothelioma and lung cancer tumour burden, therefore representing a viable therapeutic target if we can understand how they function with age and tumour suppression,” Dr Connie Jackaman from Curtin University’s immunology and cancer group says.

A comparison was made between macrophage subpopulations in C57BL/6J healthy young mice and healthy geriatric (old) mice, when exposed to mesothelioma and lung carcinoma tumour cell-derived supernatants.

The establishment of a more immunosuppressive tumour microenvironment was observed in the geriatric mice.

An immunotherapy (IL-2/anti-CD40 antibody) which eradicates tumours in young hosts, was then examined for the potential to activate macrophages in geriatric mice.

This resulted in macrophage activation that rescued T cell production of IFN-γ in geriatric mice, indicating that macrophages targeted with appropriate activation signals could rescue both age-related and tumour-induced immune dysfunction.

“Immune dysfunction is not permanent and in fact can be restored to function similarly to a young immune system,” Dr Jackaman says.

“The public may be interested to know that as they get older it is not necessarily all downhill.

“The next step for our research group is to see if we can target macrophages in a live model and induce tumour regression in elderly immune systems.”

According to the Australian Government, cancer is the leading cause of total disease burden, with 124,910 Australians estimated to be diagnosed with cancer in 2013.

The study provides a much-needed basis for further research into activating immunity in the elderly population and could eventually lead to a possible immunotherapeutic treatment for cancer.