The tumor-suppressor protein p53 plays a crucial role in cell fate decision-making. Mild and short-term DNA damage leads to p53 activation of pro-survival mechanisms, allowing the cells to repair and recover from the damage. Intensive and prolonged DNA damage triggers p53-dependent cell death to avoid the accumulation of genomic mutations.

The life and death decision-making by p53 is influenced by multiple mechanisms, including p53 post-translational modification, different binding affinities for p53 response elements, p53 threshold levels and dynamic patterns, and p53 regulation of miRNAs.

Wild-type p53 enhances antitumor immunity by sensitizing cells to immunogenic cell death, whereas mutant p53 increases mutational burden and promotes neoantigenesis.

p53-dependent anticancer immunity represents a promising direction for the development of cancer therapeutic strategies.