Study shows elderly mice with mesothelioma tumours deteriorate faster

Mesothelioma tumours in elderly mice grow faster and are more aggressive compared to younger mice, new research led by Curtin University has found.

The research, published in the journal Frontiers in Genetics, examined the role of key immune cells known as macrophages, which are found in tissues and tumours making up about 50 per cent of some cancers during ageing, and the impact this had on the growth and progression of the cancer.

First author PhD student Lelinh Duong, from the School of Pharmacy and Biomedical Sciences and the Curtin Health Innovation Research Institute (CHIRI) at Curtin University, said very few studies had examined the role of these immune cells in cancer and during immunotherapy treatment in the elderly.

“Many cancers emerge in the elderly, such as lung cancer and mesothelioma. Our immune system plays a crucial role in eliminating these cancerous cells; yet immune function usually deteriorates as we age,” Ms Duong said.

“We examined the role of these immune cells in three-month-old mice, equivalent to an 18-year-old human, compared to 24-month-old mice, equivalent to a 60 or 70-year-old human, by using an immunotherapy treatment to induce an anti-tumour response against cancerous cells.

“We found that macrophages sabotaged anti-tumour responses in the elderly, meaning that mesothelioma tumours in elderly mice were more aggressive and less responsive to immunotherapy.”

The results also showed that elderly mice with mesothelioma tumours exhibited symptoms of cancer cachexia, or wasting syndrome, which involves loss of weight, muscle atrophy, fatigue and loss of appetite, compared to younger mice.

The work was co-authored by Dr Connie Jackaman and Associate Professor Delia Nelson, also from Curtin’s School of Pharmacy and Biomedical Sciences and CHIRI.

Dr Jackaman said the research findings may help to inform future treatments for mesothelioma cancer in humans.

“These findings highlight the role of these immune cells in tumour progression during the ageing process and our research suggests that the removal of these sabotaging immune cells in elderly mice actually improved responses to immunotherapy treatments,” Dr Jackaman said.

“Our current research is examining why our immune cells change as we age and whether we can target these cells to restore immune function in the elderly. Understanding these changes could help to inform treatments in elderly cancer patients specifically.”

The research, funded by the Cancer Council WA, was also co-authored by researchers from the School of Pharmacy and Biomedical Sciences and the Curtin Health Innovation Research Institute at Curtin University, and The University of Western Australia.

The research paper, ‘Macrophage depletion in elderly mice improves response to tumor immunotherapy, increases anti-tumor T cell activity and reduces treatment-induced cachexia,’ can be found online here.

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