Related Experiment Video
Updated: Dec 29, 2025
07:47
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
2.1K
Cancer type-dependent correlations between TP53 mutations and antitumor immunity
Lin Li1, Mengyuan Li1, Xiaosheng Wang1
1Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China; Big Data Research Institute, China Pharmaceutical University, Nanjing, 211198, China.
DNA Repair
|February 3, 2020
Summary
TP53 mutations have varied effects on antitumor immunity across cancer types, influenced by tumor mutation burden and aneuploidy. This suggests TP53 status may predict immunotherapy response.
Area of Science:
- Oncology
- Cancer Genomics
- Immunology
Background:
- TP53 mutations are common in cancer and have been linked to both negative and positive effects on antitumor immunity.
- Contradictory findings necessitate further investigation into the mechanisms underlying TP53's role in anti-tumor responses.
Purpose of the Study:
- To investigate the differential impact of TP53 mutations on antitumor immunity across various cancer types.
- To explore the roles of tumor mutation burden (TMB) and tumor aneuploidy level (TAL) in mediating these effects.
- To assess the potential of TP53 mutation status as a biomarker for predicting immunotherapy response.
Main Methods:
- Analysis of five cancer cohorts from The Cancer Genome Atlas (TCGA) project.
- Comparison of antitumor immune signatures, TMB, and TAL between TP53-mutated and TP53-wildtype cancers.
- Correlation analysis between TMB, TAL, and antitumor immunity.
Main Results:
- TP53-mutated cancers showed higher immune signatures in breast invasive carcinoma (BRCA) and lung adenocarcinoma (LUAD), but lower in stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and head and neck squamous cell carcinoma (HNSC).
- TP53 mutations were associated with increased TMB and TAL, with varying relative contributions across cancer types.
- TMB positively correlated with antitumor immunity, while TAL negatively correlated, with differential impact depending on cancer type.
- Distinct correlations between TP53 mutations and antitumor immunity are driven by the combined effects of TMB and TAL.
- TP53 mutation status showed differential correlations with immune checkpoint inhibitor response across cohorts.
Conclusions:
- The effect of TP53 mutations on antitumor immunity is context-dependent, influenced by TMB and TAL.
- TP53 mutation status may serve as a predictive biomarker for cancer immunotherapy response.
- Deregulation of p53-mediated pathways may also contribute to the observed variations.
Related Concept Videos
01:27Tumor Immunotherapy
1.7K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
02:23Abnormal Proliferation
5.0K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
02:18Cancer
53.3K
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
53.3K
02:17The Tumor Microenvironment
7.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.5K
01:12Loss of Tumor Suppressor Gene Functions
5.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K