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Review

P53: A Guardian of Immunity Becomes Its Saboteur through Mutation

1
Tumour Suppression Laboratory, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne 3000, Victoria, Australia
2
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Victoria, Australia
3
Cancer Immunology Research, Peter MacCallum Cancer Centre, Melbourne 3000, Victoria, Australia
4
Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne 3000, Victoria, Australia
5
School of Health Sciences, Swinburne University, Melbourne 3122, Victoria, Australia
6
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Victoria, Australia
7
Department of Clinical Pathology, University of Melbourne, Parkville 3010, Victoria, Australia
8
Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800, Victoria, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3452; https://doi.org/10.3390/ijms21103452
Received: 27 April 2020 / Revised: 6 May 2020 / Accepted: 11 May 2020 / Published: 13 May 2020
(This article belongs to the Special Issue p53 in Cancer and beyond—40 Years after Its Discovery)
Awareness of the importance of immunity in controlling cancer development triggered research into the impact of its key oncogenic drivers on the immune response, as well as their value as targets for immunotherapy. At the heart of tumour suppression is p53, which was discovered in the context of viral infection and now emerges as a significant player in normal and cancer immunity. Wild-type p53 (wt p53) plays fundamental roles in cancer immunity and inflammation. Mutations in p53 not only cripple wt p53 immune functions but also sinisterly subvert the immune function through its neomorphic gain-of-functions (GOFs). The prevalence of mutant p53 across different types of human cancers, which are associated with inflammatory and immune dysfunction, further implicates mutant p53 in modulating cancer immunity, thereby promoting tumorigenesis, metastasis and invasion. In this review, we discuss several mutant p53 immune GOFs in the context of the established roles of wt p53 in regulating and responding to tumour-associated inflammation, and regulating innate and adaptive immunity. We discuss the capacity of mutant p53 to alter the tumour milieu to support immune dysfunction, modulate toll-like receptor (TLR) signalling pathways to disrupt innate immunity and subvert cell-mediated immunity in favour of immune privilege and survival. Furthermore, we expose the potential and challenges associated with mutant p53 as a cancer immunotherapy target and underscore existing therapies that may benefit from inquiry into cancer p53 status. View Full-Text
Keywords: cancer immunity; mutant p53; cancer immunotherapy; inflammation; gain of function cancer immunity; mutant p53; cancer immunotherapy; inflammation; gain of function
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MDPI and ACS Style

Agupitan, A.D.; Neeson, P.; Williams, S.; Howitt, J.; Haupt, S.; Haupt, Y. P53: A Guardian of Immunity Becomes Its Saboteur through Mutation. Int. J. Mol. Sci. 2020, 21, 3452. https://doi.org/10.3390/ijms21103452

AMA Style

Agupitan AD, Neeson P, Williams S, Howitt J, Haupt S, Haupt Y. P53: A Guardian of Immunity Becomes Its Saboteur through Mutation. International Journal of Molecular Sciences. 2020; 21(10):3452. https://doi.org/10.3390/ijms21103452

Chicago/Turabian Style

Agupitan, Arjelle D., Paul Neeson, Scott Williams, Jason Howitt, Sue Haupt, and Ygal Haupt. 2020. "P53: A Guardian of Immunity Becomes Its Saboteur through Mutation" International Journal of Molecular Sciences 21, no. 10: 3452. https://doi.org/10.3390/ijms21103452

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