Targeting p53 for immune modulation: Exploring its functions in tumor immunity and inflammation

p53, often referred to as the “guardian of the genome,” is a critical regulator of cellular responses to stress. p53 plays a dual role in tumor suppression and immune regulation. In addition to its well-known functions of maintaining genomic stability and inducing apoptosis, p53 orchestrates a complex interaction between innate and adaptive immune responses. This involvement contributes to pathogen clearance, immune surveillance, and immunogenic cell death (ICD). This review explores the influence of p53 on immune dynamics, detailing its effects on macrophages, dendritic cells, natural killer cells (NK), T cells, and B cells. This review explains how mutations in p53 disrupt immune responses, promoting tumor immune evasion, and highlights its regulation of inflammatory cytokines and pattern recognition receptors. Furthermore, p53's role in ICD marks it as a key player in antitumor immunity, which has significant implications for cancer immunotherapy. The review also discusses the role of p53 in inflammation, autoimmune diseases, and chronic infections, revealing its dual function in promoting and suppressing inflammation through interactions with NF-κB signaling. Therapeutically, approaches that target p53, including wild-type p53 reactivation and combination therapies with immune checkpoint inhibitors, show considerable promise. Advances in high-throughput technologies, such as single-cell RNA sequencing and CRISPR screens, provide new insights into the immunological functions of p53, including its role in microbiome-immune interactions and immune senescence. This comprehensive review highlights the importance of incorporating immunological insights from p53 into innovative therapeutic strategies, addressing existing knowledge gaps, and paving the way for personalized medicine.