Scientists have uncovered an unexpected relationship between the body’s immune system and tumorigenesis, which could prove useful for the development of future cancer interventions.
‘Tumorigenesis’ is the initial formation of a tumour in the body, whereby normal cells gain cancerous properties, such as fast proliferation and metastasis. Tumorigenesis is considered an evolutionary process, as in order to grow tumour cells must adapt to evade the body’s immune system.
In reality, naturally evolving tumours must contend with a fully functional immune system as well as the destruction of some of its cells. However, current mouse models that are commonly used to study cancer are often deficient of a full immune system. Therefore, studies that implant human tumours into mice typically lack a comprehensive and detailed view of tumorigenesis.
Tumour suppressor genes fight the immune system
Recently, a team of researchers from Howard Hughes Medical Institute uncovered a surprising new action for defective tumour suppressor genes. When functioning normally, these genes block the growth of cancer and contribute to the healthy development of cells. The scientists in this study investigated the requirements for tumorigenesis by performing in vivo CRIPSR screens of 7,500 genes in mouse tumour models, both with and without intact immune systems.
Comprehensive genetic analyses enabled the exploration of the relationship between tumorigenesis and adaptive immune selective pressures. In mice with intact immune systems, it was found that over one third of tumour suppressor genes were defective. Moreover, these mutated tumour suppressor genes triggered mechanisms that prevented the immune system from locating and destroying cancerous cells. These evasion techniques often occurred in a tissue-specific manner.
Essentially, these findings revealed that cancerous mutations are largely driven by tumours needing to avoid the adaptive immune system. Unexpectedly, tumour suppressor genes and the immune system were found to be in an evolutionary arms race battle. In fact, tumours were seen to have far more genetic tricks for fighting off the body’s defences than scientists previously thought.
The shock revelation
The conventional consensus among cancer researchers has been that when tumour suppressor genes become defective, cells just begin to grow and divide uncontrollably in an uncalculated fashion. Nonetheless, uncertainty has remained regarding why the immune system, which is normally highly efficient at attacking abnormal cells, does not fight new tumours more aggressively. This research provides an explanation for this by illustrating that many of these mutated genes have hundreds of strategies to avoid the body’s attack.
Stephen Elledge, a geneticist at Brigham and Women’s Hospital who was involved in the research, explained: “The shock was that these genes are all about getting around the immune system, as opposed to simply saying ‘grow, grow, grow’!”
There is a possibility that these evasion strategies can be examined in more detail to create interventions to block them. It is hoped that insights gained from further research could be used to treat cancer in the future. For example, checkpoint inhibitor drugs treat cancer by hyper-activating the immune system. However, these drugs are not used universally as many are only effective for a minority of patients and cancer types. These new findings could open doors for improving the efficiency of such cancer drugs and uncover completely novel ways to overcome tumour evasion tricks.
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