Tumors and stuff - Part 2!

Written By Vaishnavi Kolluru

Tumors part 2! Thanks everyone for all the interest in the last article :) Creds @Epipen, @Calnexin, @Bankman for inspo. I'm learning a lot! <3

My previous article is an introduction to tumors!! Check it out if you haven't already.

Tumors are characterized by abnormally rapid growth and compromised genetic material. Surrounding the tumor is the stroma, which consists of various supporting cells (leukocytes, fibroblasts, smooth muscle, endothelial cells, etc). Stromal cells help tumors grow and spread. For example, stromal cells secrete signaling molecules that promote tumor growth and ECM remodeling. Tumor cells remodel the stroma and ECM as well. As you can see, this is a positive feedback-based communication between tumor and stromal cells. Eventually, the tumor cells and stromal cells develop a mutual dependence, kind of like a symbiotic mutualism, further highlighting the central role of the tumor microenvironment in cancer pathogenesis.

One phenomenon that affects the tumor microenvironment is the Warburg Effect, which describes the metabolic shift when a cell becomes cancerous. The Warburg Effect describes the phenomenon of cancer cells utilizing only fermentation pathways even in the presence of oxygen. Many driving factors for this switch have been proposed, but none have yet been solidly confirmed. However, the consequences of the Warburg Effect are well-established. Warburg affects the TME by promoting angiogenesis (so there's more blood and nutrient supply to the tumor), exerting immunosuppressant effects (to allow tumor growth to occur undetected), and increasing fibroblast formation (to reduce immune cell entry and "hide" from chemotherapeutic drugs). These effects are exerted by certain metabolites from the anaerobic fermentation, as well as other molecules that are upregulated in tumors. 

Another phenomenon that relates to the function of TME immune cells is cancer immunoediting. Immune cells have differential success with different groups of cancer cells in the body. The ones that survive our immune attack have more growth than the other tumor groups in the body. It's kind of like natural selection, but within your body, and between groups of cancer cells. Tumor growth is also promoted by their release of immunosuppressants. This further hinders defense against cancer. 

Let's talk about how to attack cancer cells via immune cells: chimeric antigen receptor (CAR) T-cell therapy. This therapy modifies patient T-cells in vitro by adding a chimeric (from multiple places) antigen receptor, making them CAR T-cells. These cells behave similarly to our own body's immune cells as they target the foreign cancer cells. However, they require a certain set of conditions. First, our own immune cells must be suppressed so that they don't recognize the CAR T-cells as foreign. Additionally, we need a good amount of cancer cells to be present so the CAR T-cells have something to work with initially. To achieve these effects, we can use a little bit of chemotherapy for immunosuppression,  while not overdoing it so as to prevent loss of too much cancer.

That's it for this week. Do y'all want a part 3? Any other topic suggestions? Let me know in the comments / my DM (@humblehornworth)!!

Here are some extra resources to learn more about this topic:

Vaishnavi Kolluru
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The Ames Test
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Understanding Cancer's POV - The Tumor Microenvironment