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Tumor microenvironment 101: we fight cancer but cancer fights back

posted: April 8th, 2019

As the leading cause of death in Canada, cancer is a feared yet very common diagnosis1. In 2017 alone, a frightening $5,636.4 billion was invested into cancer research in the United States of America, yet the “cure to cancer” remains evasive2. For those of us who do not believe in conspiracy theories claiming that cancer research is in fact a lucrative capitalist ploy, we wonder why cancer is so difficult to treat successfully.

 

Much of the aforementioned funding is used to support research to characterize cancer (as the saying goes, know your enemy). There are a multitude of reasons cancer is so unresponsive to treatment; it is a heterogeneous disease with an unclear etiology that is ever evolving and difficult to identify.

 

Cancer occurs when human tissues cells mutate and proliferate uncontrollably. Cellular mutations are quite common. However, a function of the immune system known as immunosurveillance identifies and eliminated these mutated cells before they are able to cause harm. As such, our immune system is the first line of defense against cancer development. When immune tumour suppressing mechanisms fail, a tumour develops. Once again, the immune system intervenes to control tumour progression. In fact, many promising tumour therapies harness the power of the immune system. However, while we attack the tumour, the tumour fights back by editing its microenvironment to evade the immune system. The “tumour microenvironment” is an adaption that promotes cancer growth and survival through various mechanisms, briefly outlined below.

 

Some known characteristics of the tumour microenvironment:

 

  • Angiogenesis: As a tumour grows, the centre of the tumour often starts to lack oxygen. A tumour can actually induce the formation of vasculature in and around itself to improve nutrient and oxygen delivery, promoting growth as well as a pathway for metastasis to spread3.

  • Effector T cell inhibition: Effector T cells are able to infiltrate the tumour and kill tumour cells. However, tumour associated macrophages, regulatory T cells and myeloid-derived suppressor cells that are abundantly present in the tumour environment release and upregulate inhibitory molecules and enzymes that disable the effector T cells4.

  • Immature dendritic cells: Mature dendritic cells are the first step to initiating an adaptive immune response. They activate T cell and B cells which help get rid of threats. However, tumours can produce various molecules that block the maturation of dendritic cells, rendering them dysfunctional4.   

  • Downregulation of recognition signals: Tumour cells downregulate cell surface markers so that immune cells can no longer recognize and target tumour cells 4.

  • Increase inflammation: The tumour microenvironment can direct infiltrating white blood cells to produce a special type of inflammatory cytokines which can upregulate genes responsible for cell proliferation, thus helping tumour growth4.

  1. "Cancer Statistics at a Glance - Canadian Cancer Society." Www.cancer.ca. Accessed March 30, 2019. http://www.cancer.ca/en/cancer-information/cancer-101/cancer-statistics-at-a-glance/?region=ab.

  2. "Research Funding." National Cancer Institute. December 2018. Accessed March 30, 2019. https://www.cancer.gov/about-nci/budget/fact-book/data/research-funding.

  3. Nishida, Naoyo, Hirohisa Yano, Takashi Nishida, Toshiharu Kamura, and Masamichi Kojiro. "Angiogenesis in cancer." Vascular health and risk management 2, no. 3 (2006): 213.

  4. Whiteside, T. L. "The tumor microenvironment and its role in promoting tumor growth." Oncogene 27, no. 45 (2008): 5904.