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Viral Signs for Immunotherapy

Written by Christina Young and Edited by Mehr Bawa

Image by Colin Behrens from Pixabay 

While many vaccines and drugs are attributed to curing disease, they may also assist your body’s own defense mechanism, the immune system. The immune system is a web of pathways that protect you from invading pathogens like viruses and bacteria, and help to make a distinction between your own cells and invading pathogens, known as self versus non-self recognition.

One of the most prevalent diseases that blurs the immune system’s distinction between self and non-self is cancer, masses of one’s own non-functional cells that accumulate. Since cancer tumors are composed of one’s own cells, they have the ability to escape attack by the immune system and continue to cause harm to one’s body [1]. In 2017, cancer affected approximately 15 million individuals in the U.S. alone, and will be the cause of an estimated 600 thousand deaths by the end of 2020 [2]. Many cancer therapies include radiation and chemotherapy, which are invasive procedures that weaken patients’ immune systems, making them unable to fight off other diseases and leaving them at a higher risk of other infections even after tumor removal [3] [4]. In recent years, scientists have sought ways to enable the immune system to fight off cancer formation without the use of these invasive actions by understanding the mechanism and relationships between the immune system and solid cancer tumors, which are hard to penetrate with many types of cancer treatments.

The immune system consists of two different branches: adaptive and innate. These branches work in tandem to fight off pathogens and differentiate between self and non-self cells. The innate immune system is the body’s non-specific, first response to disease-causing agents and includes cells that actively destroy pathogens. Most disease-causing agents are unable to get past the innate system, but when they do, the adaptive immune system comes into play, learning and creating a specific reaction to the pathogen that is remembered and can be activated quickly if the pathogen is encountered again [5]. One type of cell involved in the adaptive immune system are memory T cells, which help recognize previously encountered pathogens. These cells function like recognizing a person by their clothes and are quick in eliciting a reaction to attack the disease-causing agent. They constantly travel and patrol the body for harmful agents, and most interestingly, even check some solid cancer tumors for virus infection [6].
By taking advantage of these aspects of memory T cells, the Rosato lab in 2019 has looked into putting viral parts into tumors to attract corresponding memory T cells. By dressing up tumor cells as cells infected by a virus, memory T cells would then be encouraged to enter the tumor and signal an immune response to fight off the “infection.” Testing across two different viruses and a viral mimic, researchers observed that when these viral components were injected into a mouse model of skin cancer, memory T cells were better attracted to the tumors and elicited strong immune system activation to the site, evidenced by a threefold increase in the number of other immune system cells attracted to the tumors following memory T cells [7]. This response directed to the tumor has the potential to both kill the tumor cells present and recognize tumor cells to prevent possible reactivation of the disease later on. Although having not progressed to clinical trials at the moment, the use of virally directed T cells to a tumor is promising to help cell-based immunotherapies directed to target solid tumors [3].

References

  1. “What is Cancer?” National Cancer Institute, National Institute of Health. 2015. https://www.cancer.gov/about-cancer/understanding/what-is-cancer
  2. “Cancer Stat Facts: Cancer of Any Site.” National Cancer Institute, National Institute of Health. 2019.https://seer.cancer.gov/statfacts/html/all.html
  3. Schirrmacher, V. (2018). From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment. International Journal of Oncology. 54:407-419
  4. Freida Wiley. “Complications of Solid Tumors and Treatments.” Drug Topics, MJH Life Sciences. 2019. https://www.drugtopics.com/view/complications-solid-tumors-and-treatment
  5. “The innate and adaptive immune systems.” Informed Health, Institute for Quality and Efficiency  in Health Care (IQWiG). 2016. https://www.ncbi.nlm.nih.gov/books/NBK279396/
  6. Martin, M.D., Badovinac, V.P. (2018). Review: Defining Memory CD8 T Cell. Frontiers in Immunology. 9: 1-10. https://www.frontiersin.org/articles/10.3389/fimmu.2018.02692/full
  7. Rosato, P.C., Wijeyesinghe, S., Stolley, J.M., Nelson, C.E., Davis, R.L., Manlove, L.S., Pennell, C.A., Blazar, B.R., Chen, C.C., Geller, M.A., Vezys, V., Masopust, D. (2019). Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nature. 10:1-9. https://www.nature.com/articles/s41467-019-08534-1
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