The Cancer Microenvironment: What Conditions Do Tumors Thrive in?

In general, there are risk factors for cancer that we should avoid from our environment. Focusing further inside our body, we can investigate the kind of microscopic environment cancer cells need. There are different types of cancers. Each of these responds specifically to different parts of our bodies. In an attempt to understand this specific environment, we will explore the tumor microenvironment. This refers to the specific conditions inside our bodies that may support cancer cell proliferation. Throughout the discussion, we will see how different parts of our body can change to promote cancer cell growth. 


Macroscopic Cancer Environment

There’s really no need to call it a “macroscopic” cancer environment. This simply refers to the actual living conditions you are currently in and the cancer risk factors we can get from the environment.

While each type of cancer is very particular, the National Cancer Institute (NIH) has noted general risk factors for cancer. The following are some suspected risk factors for cancer:

  • Age: it is an undeniable trend that cancer risk increases as a person grows older.
  • Alcohol: research shows that there is a higher risk of cancer the more you drink.
  • Obesity: conversely, the pair of a healthy diet and an active lifestyle reduces the risk of cancer.
  • Tobacco: this can cause damage to one’s DNA, especially in the mouth, larynx, esophagus, and lungs.
  • Carcinogens: the NIH provides a list of these cancer-causing substances. 

These risk factors are the results of epidemiological studies. These studies take a great amount of data into account and analyze it to make conclusions. This means that scientists listed these risk factors through statistics. It does not consider the actual mechanisms at play on how they specifically increase cancer risk. This is why these are still called “suspected” risk factors. To know the biological basis of cancer, we must delve deeper into the tumor microenvironment. 


Microscopic Cancer Environment

Our body functions at an incredible rate of specificity. If we take a look at our tissues, each and every component serves a function. When a cancer cell tries to invade a part of our body, it can modify the surrounding tissues to its benefit. This means that cancer cells also operate at a very specific mechanism.

There are many ways for a cancer cell to proliferate in our own body’s cellular environment. It can be through bypassing immune checkpoints, altering our microbiome, and even creating its own blood supply. Cancer cells may trigger these processes. Sometimes, our own bodies induce it.

As previously discussed, each cancer type operates differently depending on the site. This is mostly because each cancer microenvironment is different from another. Specifically, we will be investigating the tumor microenvironment of the breast, colorectal, and blood cancer cells. 


Immune Checkpoints in Breast Cancer

Since cancer is a foreign body within our system, it triggers a response from the immune system. An immune response undergoes activation of immune checkpoints to function. This allows immune cells to traverse through the body at a controlled rate. In the case of breast cancer invasion, certain factors inhibit or bypass these immune checkpoints.

Several immune cells will surround the tumor microenvironment of breast cancer as the body’s immune response. These immune cells include the T cells, dendritic cells, and B cells from the adaptive immune response. Lymphocytes are special T cells considered as one of the key immune cells against cancer cells. In addition, the macrophages, neutrophils, eosinophils, and natural killer cells from the innate immune response also participate. 

Non-immune cells also surround and affect the tumor microenvironment. Fibroblasts are cells that support the structure of our connective tissues. Essentially, it holds our organs and tissues in place. These can become cancer-associated fibroblasts when surrounding cells alter their function. Intuitively, the cancer cells are responsible for its alteration. However, our own epithelial and endothelial cells can also alter the fibroblasts to benefit the cancer cells. 

One characteristic that helps the proliferation of breast cancer cells is its epithelial-mesenchymal transition. It allows cancer cells to gain the properties of normal mesenchymal cells and bypass immune checkpoints. Breast cancer cells induce this transition through factors such as Snail, Twist-1, and Lox transcriptions.


Microbiota of Colorectal Cancer

Aside from the immune system, colorectal cancer cells need to deal with the competitive gut microbiota to thrive. Our gut microbiome is an innate system in our digestive system that normally aids in our body’s functions. As cancer cells infiltrate the colorectal system, they alter the gut microbiome in a process called dysbiosis.

The association between the gut microbiome and colorectal cancer started in 2011. Scientists saw an alarming number of a bacterium called Fusobacterium nucleatum in colorectal cancer patients. From then on, research on the difference between a healthy gut microbiome and those with colorectal cancer continued.

Over time, researchers saw a stage-dependent variation in the gut microbiome. Some species increase depending on tumor development in the patient. These species include the Fusobacterium nucleatum, Peptostreptococcus anaerobius, and Lactobacillus sanfranciscensis

On the other hand, some species seem to aid in blocking tumor proliferation and infiltration. These include bacteria from the genera Alloprevotella, Treponema, and Desulfovibrio. From this, we can really see the adverse effects of the gut microbiome in colorectal cancer. 


Endothelial-Leukemia Interactions

As cancer cells begin to invade and clump up, they need their own blood supply. Cancer cells do this by aggressively modifying the tumor microenvironment to perform angiogenesis. This process manages specific activator and inhibitor molecules to create new blood vessels around the tumor. 

In a recent study published in August of 2022, it appears that endothelial cells in blood vessels interact with T-cell acute lymphoblastic leukemia. Endothelial cells alter drug responses to aid tumor cells to mitigate the damage. This means that endothelial cells provide a pro-tumorigenic response against our own body. 

This is a reason why 30% of T-cell lymphoblastic leukemia treatments fail. Researchers hope to use this discovery to work around this tumor microenvironment. They are testing different drug treatments that bypass this effect from the endothelial cells.

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