Enhanced Immune System Activity Prevents Tumor Growth in Aged Mice

Results obtained from studies carried out on mice indicate that it may be possible to stimulate the immune system of elderly individuals so that they become able to respond to anticancer therapy in a manner similar to younger subjects.

Modulating the activity of T regulatory (Treg) cells, which are components of the immune system that suppress immune responses of other cells and act as an important “self-check” built into the immune system to prevent excessive reactions, has been shown to increase the success of chemotherapy in young subjects but not in their elderly counterparts.

To explain this finding, investigators at the University of Texas Health Science Center (San Antonio, USA) worked with selected young and aged mouse populations. They confirmed that depletion of Tregs improved immune response in young animals without benefiting the elderly mice. However, results published in the April 15, 2012, issue of the journal Cancer Research, explained the reason for this.

Depletion of Treg activity in the elderly mice caused a massive increase in another type of immune suppressor cell: myeloid-derived suppressor cells (MDSCs). These cells, which do not proliferate in the young animals, maintained the relative inefficiency of the aged immune system. Treating the aged mice with both a drug to block Treg activity and a monoclonal antibody that caused MDSC depletion improved tumor-specific immunity and reduced melanoma tumor growth in the aged mice.

“We have shown that an aged immune system can combat cancer just as well as a young one if you remove the impediments to successful immunity, which are different that those in younger hosts,” said senior author Dr. Tyler Curiel, professor of medicine at the University of Texas Health Science Center. “We have shown that if you test all your immune therapy just in young mice and young people, you will never learn how it works in older patients — the ones most at risk for cancer. You might conclude that drugs do not work in aged hosts, when they do. But they have to be combined with some help.”

While this approach was successful for treating melanoma, a different monoclonal antibody was required for colon cancer.

“The details were different in colon cancer. The bad immune cells that increased in the aged mice and how they were knocked down by the drugs were different than in melanoma,” said Dr. Curiel. “But the result was the same — we identified a drug combination that was highly effective in the aged mice. It is a bit complicated, but it is possible to put into practice, and because these approaches could be so much more specific and so much better tolerated than conventional chemotherapy, it is well worth pursuing.”

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