Abstract Text: How the human immune system interacts with a tumor before diagnosis is almost entirely unknown. Here we analyzed a longitudinal cohort of 133 healthy individuals (from 18 to over 90 years old), 28 of whom developed cancers over nine years. We found that a large group of cytokines surges 2-3 years before a cancer diagnosis, but not with other conditions (such as inflammatory or cardiovascular diseases). And these cytokine surges precede a cancer diagnosis only in those 80 years or older. In the The Cancer Genome Atlas (TCGA) we found that from 1,741 tissues across 8 types of cancers, elderly individuals elevate the transcription of a broad set of cytokines (including IFNG, IL1B, IL15 and others). Defects in cellular senescence (TP53 or CDKN2A/p16 mutations) sensitize the cells for the inflammation associated with advanced aging. Advanced aging elevates IRF1, a p53 and p16-independent transcription factor for apoptosis and inflammation. The rise of cytokine transcription in early-stage cancer tissues thresholds at the age of 80 years, similar to our serum findings.
