The thymus undergoes age-related atrophy, coincident with increased circulating sex steroids from puberty. The impact of thymic atrophy is most profound in clinical conditions that cause a severe loss in peripheral T cells with the ability to regenerate adequate numbers of naive CD4+ T cells indirectly correlating with patient age. The present study demonstrates that androgen ablation results in the complete regeneration of the aged male mouse thymus, restoration of peripheral T cell phenotype and function and enhanced thymus regeneration following bone marrow transplantation. Importantly, this technique is also applicable to humans, with analysis of elderly males undergoing sex steroid ablation therapy for prostatic carcinoma, demonstrating an increase in circulating T cell numbers, particularly naive (TREC+) T cells. Collectively these studies represent a fundamentally new approach to treating immunodeficiency states in humans.

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Background ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. Methods 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. Results 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). Conclusions In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group.

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days respectively. Patients with an immune-related adverse event survived longer than patients with no immune-related adverse event, with a mean of 208 versus 88 days. CyTOF analysis showed patients with a systemic PR after SBRT had a population of CD8+ CD127-Ki-67+ CD45RO+ T cells that correlated with response. Conclusion: The addition of SBRT after progression on immunotherapy resulted in increased PFS, a systemic response rate of 9.52%, and a disease control rate of 57.14%. Improved PFS correlated with an increased TIL score, the presence of an immune-related adverse event, and T cell activation status.