Male mice lose cancer-fighting immune cells earlier with age

Researchers from Massachusetts General Hospital, publishing in Nature Aging, investigated whether sex differences in immune aging could help explain why men face higher cancer rates. They focused on naive CD8+ T cells: immune cells that have not yet encountered a threat and stand ready to recognize tumors. A diverse pool of these cells is essential for broad immune protection.

What the mouse experiments showed

The researchers implanted melanoma cells into young and middle-aged mice. In young animals, tumor growth was similar between males and females. But middle-aged male mice controlled tumors less effectively than same-age females. When CD8+ T cells were depleted, this sex difference disappeared. The researchers identified lymph nodes as the source of the stronger female immune response.

Tumor-draining lymph nodes in middle-aged female mice contained more activated and tumor-specific CD8+ T cells. There was no evidence that these cells divided faster. Antigen uptake and presentation by immune cells also did not differ significantly between sexes. The problem appeared to lie in the supply of naive CD8+ T cells available to begin with.

Males lose these cells earlier

Cell counts confirmed a substantial age-related loss of naive CD8+ T cells. Male mice began losing these cells earlier than females. Analysis of existing human blood datasets suggested a similar sex-biased pattern. CT scans also showed smaller lymph nodes in men.

Restoring thymic activity, which is where naive T cells are produced, improved tumor protection in the mice. Whether this translates to humans was not tested in this study. The findings offer a preliminary biological explanation for higher cancer incidence in middle-aged men.

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