Lymph node shrinkage limited cancer recognition in male mice

In experiments in mice, males lost naive CD8 T cells—immune cells not yet activated by their specific target—earlier than females. They shifted faster into virtual memory cells, which had memory-like features without encountering their target. Shrinkage of the thymus, the organ where T cells mature, also limited replacement of naive cells.

Together, these changes led to faster shrinkage of lymph nodes, small organs where immune cells gather, in males. Fewer distinct groups of naive T cells remained locally available, limiting recognition of cancer targets. Androgen ablation—removal or suppression of male sex hormones—regenerated the thymus in male mice. This replenished naive cells in lymph nodes, strengthened cancer-specific T cell responses and improved responses to immune checkpoint blockade, a cancer therapy that releases brakes on immune cells.