P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future
Open accessAbstract
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.
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Gene mutations, including those affecting undruggable proteins, have a significant impact on the efficacy of cancer immunotherapy.
“It is widely accepted that gene mutations, including those affecting undruggable proteins, have a significant impact on the efficacy of cancer immunotherapy.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [611]
Mutations can affect the tumor immune microenvironment by altering cytokine expression and regulating the tumor's sensitivity to immune checkpoint inhibitors.
“These mutations can affect the tumor immune microenvironment (TIME) by altering cytokine expression and regulating the tumor’s sensitivity to immune checkpoint inhibitors.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [611]
Cancer cells with functional wild-type genes tend to have a cancer-restrictive tumor immune microenvironment, while an imbalance in their expression can create a cancer-supportive tumor immune microenvironment.
“For examples, cancer cells with functional wild-type genes tend to have a desirable cancer-restrictive TIME, while an imbalance in their expression can create a cancer-supportive TIME.610,611”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [611]
The status of genes can influence tumor cells through the impact of wild-type gene loss and through their effects on the tumor immune microenvironment.
“In brief, the status of genes can influence tumor cells not only through the impact of wild-type gene loss but also through their effects on the TIME.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [611]
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- Authors
- Levine, A. J.
- Affiliations
- Institute for Advanced Study (US)
- Corresponding author
- Levine, Arnold J.
- ORCID
- Levine, Arnold J.
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 541
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7013403
- OpenAlex
- W2999295144
- Cited by
- 97
- References
- 39
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 10 · 2023: 22 · 2022: 21 · 2021: 19 · 2020: 10
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Cancer Institute (P01CA087497)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- p53, immune response, innate immunity, adaptive immunity, cancer immunotherapy, tumor antigens, CD8+ T cells, B cell antibody response, senescence, aging, autoimmunity, inflammation, neurodegeneration, epigenetic stability, tissue regeneration, tumor-specific transplantation antigen
- MeSH terms
- Aging, Antigens, Neoplasm, Humans, Immunity, Innate, Immunotherapy, Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Adaptive Immunity
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