Senescent CD8 T effector memory cells are functionally impaired, enriched in aging and disease, and a barrier to immunotherapy.

SA-βGal high CD8 T effector memory cells in humans increase with age and are functionally impaired, showing reduced proliferation, cytokine production, and senescent-cell elimination.

• Why it matters: Senescent cells accumulate systemically with aging, but it is unclear whether CD8 T effector memory cells themselves become senescent and how that affects immune control and immunotherapy.
• What they did: Using single-cell RNA sequencing, the study mapped SA-βGal high CD8 T cells across differentiation stages, then tested their proliferation, cytokine output, and ability to eliminate senescent human stromal cells.
• The result: Senescence-associated gene signatures in SA-βGal high CD8 T EM cells are enriched in older donors, age-related disorders, cancer, and smokers, and senescence is distinct and dominant over exhaustion, limiting checkpoint blockade responses.

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