Role of Mutated Tumor Suppressor Genes in Facilitating Cancer Cells Avoidance of the Immune System

Cancer contributes significantly to the disease burden in the USA and it is also one of the leading causes of disease and death. According to the National Cancer Institute estimations, about 1,806,590 new cases of cancer will be diagnosed in the US in 2020 and 606,520 people will possibly die due to cancer. Given its high impact on the population in terms of causing disease and financial strain, it is an area of rigorous research.Cancer

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Cancer research aims to study the molecular mechanisms of its development to highlight targets for possible ways to detect and treat it in its early development and reduce its impact on individuals as well as populations. Many great advances have been made in understanding its molecular basis and mechanisms of its development and there is ongoing research in various aspects to better understand and treat various types of cancers.

A paper was recently published that examined the role of tumor suppressor genes in facilitating evasion of the immune system. Scientists concluded that mutations in these genes can lead to cancer cells avoiding the attack of the body’s immune system and hence, avoid destruction by the body’s defense mechanism. This is an important step in understanding the mechanism of carcinogenesis and evasion of the immune system by tumor cells.

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Previously, it was believed that mutations in tumor suppressor genes lead to unregulated cell growth in cancer cells. But this explanation did not hold weight when these genes were put in a petri dish to see if they cause unregulated growth. It didn’t result in unregulated cancer cell growth. Moreover, it was not clear how cancer cells avoid being targets of the immune system.

The published paper aims to answer these questions. The research team behind this paper studied the effects of 7500 genes that included genes that are believed to be involved in the development of cancer. The team learned that mutations in the genes involved in carcinogenesis trigger few mechanisms that help the cancer cells avoid the attack of the immune system.

Findings of the Study

The team used CRISPR engineering to modify thousands of cancer cells that resulted in each cell having one defective gene. These cells were put in two types of mice, one with a functioning immune system and the other without a functioning immune system.

The researchers then did a genetic analysis that showed that the tumor suppressor genes were found frequently in mice with functioning immune systems. After finding that, the team focused on a specific gene named GNA 13 that, when mutated, helped cancer cells evade the immune system’s T cells.

The researchers believe that it is a possibility that these mutated genes may be acting through similar mechanisms.

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Future direction

The researchers believe that future research will clarify if these mutated tumor suppressor genes are acting through similar mechanisms. If that is the case, it might be possible to research pharmaceutical agents that can block these mechanisms that will lead to the prevention of evasion of immune attack by tumor cells. Eventually, it may result in hampering carcinogenesis.

This published paper not only points towards new possibilities of treating cancer but also, directing research towards studying new mechanisms involved in carcinogenesis. Although it has been known for some time that cancer cells avoid the attack of the immune system, this research points towards specific mechanisms underlying this evasion and possibly, opening doors for enhancing understanding specific molecular pathways involved in avoiding the immune attack by cancer cells and also, steering pharmaceutical research in this direction.

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Authors

This paper was published in the journal Science by Stephen J. Elledge, Mamie Z. Li, Anthony C. Liang, Ajinkya Patil, Mei Yuk Choi, Timothy D. Martin, Rupesh S. Patel from Division of Genetics, Howard Hughes Medical Institute, Harvard Medical School, and Danielle R. Cook and Kevin M. Haggis from the Department of Cancer Biology from the same medical school.

References

What is cancer research? American association of cancer research, Accessed October 4, 2021, https://www.aacr.org/patients-caregivers/about-cancer/what-is-cancer-research/

Cancer Statistics, National Cancer Institute, Accessed October 4, 2021, https://www.cancer.gov/about-cancer/understanding/statistic

The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation, Science, Accessed October 4, 2021, https://www.science.org/doi/10.1126/science.abg5784

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