Macrophages and the Immune System

The varied and interesting role that macrophages take in tumor growth—or suppression—is a widely researched and debated topic. A macrophage is a type of white blood cell, which is part of your immune system. The human immune system is responsible for identifying, destroying, and removing all foreign substances from the body. However, macrophages are very malleable and take varied roles in the growth and spread of cancer cells.

Macrophages begin as monocytes and are produced in your bone marrow. As these white blood cells mature and get released into your bloodstream they travel to and are stored within your spleen, lymph nodes, tonsils, or in your liver. When damage, infection, or even injury triggers a response, the monocytes leave their primary location and travel through the bloodstream to enter other tissues and organs in the body. After leaving the bloodstream, monocytes develop into macrophages.

In the big picture of things, macrophages can ingest and destroy bacteria, clean up cellular debris and other harmful particles, as well as dead cells that contain microbes, such as bacteria or viruses. After macrophages ingest these dead cells, they will take some of the material from the microbe inside the cell—a snapshot of the intruder if you will—and present it to other cells in the immune system. In this way, macrophages can "sound the alarm" that a foreign invader is in the body and help other immune cells recognize that invader.

In the presence of cancer, macrophages have different functions, the implications of which are still being explored. Once they travel via the blood inside a tumor, they turn into tumor-associated macrophages or TAMs. Although the purpose of a macrophage is to destroy and remove foreign invaders—such as the cancer cells that make up the tumor—we have discovered that varied factors ​change the macrophages normal response at this point.​

Typically, if your tumor has a high number of TAMs within, it is usually a very poor prognostic sign, which means that the cancer is very likely to metastasize, or spread to other tissues in your body. For reasons outside the scope of this article, some of the macrophages stop doing what they are intended to do inside the tumor and start to help the tumor grow and spread. Research has also shown that these TAMs, unlike their counterparts outside of the tumor, are less likely to notify your immune system of the cancer presence, which delays reinforcements from your immune system.

This is where the role of macrophages gets really interesting. In recent studies of the immune response to colorectal cancer, it is found that the TAM cells mutate even further into two different types of macrophages: M1 and M2 types. Whereas the M1 type continues to fight colorectal cancer cells, the M2 has been found to actually help promote its tumor growth, metastasis, and regrowth.

Although this sounds like horrible news—the very cells intended to protect and heal your body and now helping cancer grow—research is focusing on how to stop the macrophages from mutating at a key point in the immune response. If this research comes to fruition, new drug therapies could be formulated to help stop metastasis, keeping colorectal cancer local, where it is far easier to treat.

Studies to learn more about potential applications of TAMs in colorectal cancer are ongoing. Current research is focused on using the immune response—specifically the chain of events that occurs when cancer begins—and how to stop our immune system from potentiating the colorectal cancer metastasis.