Humans and chimpanzees share a close evolutionary relationship, genetically linking us. As a result, the two species can pass on infection and disease to one another. The world is full of potential pathogens that can cause deleterious effects, and researchers are investigating how to limit and stop cross-species disease interaction. Some diseases spread faster or slower than others. This is mostly due to human-chimpanzee proximity and disease transmission. However, some diseases cannot be transferred even within a species, such as cancer. Researchers recently found that chimpanzees do not get cancer as often as humans. Interestingly, even though humans and chimpanzees share over 98% of genetic code, chimpanzees have a lower rate of cancer than humans.
Many different factors play into why humans have greater risk of cancer than chimpanzees. Besides genetic differences, DNA accessibility and environmental factors are crucial components that dictate cancer susceptibility. DNA accessibility refers to the available DNA that can be transcribed and translated into proteins that the body needs. If the wrong proteins are made, issues can arise where cells become dysregulated. Environmental factors refer to diet, smoking, and other lifestyle habits that increase risk of cancer.
Cancer is the uncontrollable cell growth of malignant, highly mutational cells throughout the body. While there are treatments, the site of cancer, the aggressive nature of a tumor, and its progression (or stage) all determine treatment plan. Additionally, different mutations and surface proteins can act as biomarkers to predict therapeutic outcomes. Currently, scientists are trying to understand on a cellular level, what specifically reduces the risk of cancer in chimpanzees compared to humans.
A recent article in Nature Communications, by Dr. Jogender Tushir-Singh and others, discovered an evolutionary change between humans and chimpanzees that helps explain why immune cells are less equipped to fight cancer. By studying chimpanzees and comparing their biology to humans, we have the potential to improve current immunotherapies. Tushir-Singh is an Associate Professor at the University of California, Davis (UC Davis) School of Medicine. His work primarily focuses on protein engineering and improving cancer therapy with multi-targeting of antibodies. Specifically, Tushir-Singh engineers specific T cells that can infiltrate tumors and improve immune cell response.
The genetic difference or change was in an immune cell protein known as Fas Ligand (FasL). Unique to humans, FasL can become disabled by a tumor-associated enzyme known as plasmin. This evolutionary mutation is suggested to have contributed to larger brain size in humans. However, it is an unfavorable tradeoff in the context of cancer since this mutation prevents immune cells from properly targeting tumor growth. FasL is critical to eliminate cells and is directly involved in cell death. Immunotherapies, including engineered therapies have used FasL to destroy cancer cells. Unfortunately, since FasL is disabled in the context of cancer, immune cells are neutralized and lack effective immunity.
The discovery made by Tushir-Singh and others helps explain the limitations of immune cell-based therapies. By restoring FasL activity, researchers can improve treatment and limit tumor progression. In addition, combining FasL immunotherapy with another cancer treatments may be able to boost immune response in patients and prolong overall survival in refractory tumors.
Article, Nature Communications, Jogender Tushir-Singh, UC Davis