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Abstract
The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.
Highlights
Forty years ago, four research groups in London, Paris, New York City/Bethesda, MD, and Princeton, NJ, USA, discovered the p53 protein in a variety of cancerous cells and normal cells employing antisera from animals carrying SV40 virus-induced tumors or spontaneously-derived tumors [1,2,3,4]
Lloyd Olds was a noted tumor immunologist, David Lane had just completed a PhD in the laboratory of an immunologist, and Arnold Levine taught immunology courses at Princeton University, so the authors of the first papers might have pursued the role of the p53 protein in adaptive and innate immunity, and in cancer biology
Eubacteria and Archaea have developed various Crispr systems, while invertebrates employ macrophage-like cells to eliminate bacteria, and have an innate immune system
Summary
Four research groups in London, Paris, New York City/Bethesda, MD, and Princeton, NJ, USA, discovered the p53 protein in a variety of cancerous cells and normal cells employing antisera from animals carrying SV40 virus-induced tumors or spontaneously-derived tumors [1,2,3,4]. These observations began a set of studies on the role of p53 in cancers that has led to the conclusion that p53 mutations are the most common feature of human cancers. If 50% of human cancers have p53 mutations, and if the immune system recognizes foreign tumor antigens targeting them for cellular rejection, these two lines of research will make a good marriage
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