Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment.
The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome.
['Cui|Yan|Y|', 'Guo|Gang|G|']
D000970:Antineoplastic Agents D017209:Apoptosis D063646:Carcinogenesis D016207:Cytokines D015972:Gene Expression Regulation, Neoplastic D006801:Humans D007093:Imidazoles D057131:Immune Evasion D009154:Mutation D016328:NF-kappa B D009369:Neoplasms D010879:Piperazines D051736:Proto-Oncogene Proteins c-mdm2 D015398:Signal Transduction D051193:Toll-Like Receptors D059016:Tumor Microenvironment D016159:Tumor Suppressor Protein p53
tumor suppressor p53 tumor microenvironment p53 inactivation inflammation adaptive antitumor immunity immune suppression immunotherapy innate immunity