What Is a Macrophage? Types and Functions? Friend or Foe in Cancer?

Many immune system cells participate in defending the body against pathogens. Macrophages, one of the immune system’s white blood cells, have an important role in the body’s defenses.

What is a macrophage?

Research shows that macrophages differentiate from circulating monocytes in response to signals generated by pathogens (such as microbes).

The name macrophage comes from Greek and means big eater (makros = large; phagein = to eat).

What are the functions of macrophages?

Macrophages take cellular waste, foreign substances, microbes, cancer cells and anything lacking proteins characteristic of healthy body cells on its surface and, through a process called phagocytosis , engulf and digest them. These large eating cells are found in essentially all tissues.

Why are macrophages important for COVID-19 vaccines?

To understand how COVID-19 vaccines and vaccines in general work, it helps first to consider how the body fights disease. When microbes such as bacteria or viruses enter, they attack and multiply. This invasion, called infection, causes disease. The immune system uses various tools to fight it. Blood contains red blood cells carrying oxygen to tissues and organs and white immune cells fighting infection. These white cells primarily include macrophages, B lymphocytes and T lymphocytes:
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Macrophagesleave behind parts of invading microbes called antigens. The body identifies antigens as dangerous and stimulates antibodies to attack them. Macrophages are the first immune cells to process / encounter viral antigens contained in vaccines.
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B lymphocytesproduce antibodies attacking the antigens left behind by macrophages.
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T lymphocytesare another type of defensive white blood cell. They attack body cells already infected.

Vaccines help develop immunity by imitating an infection. This type of infection almost never causes illness, but prompts the immune system to produce T lymphocytes and antibodies. Once the imitation infection disappears, “memory” T lymphocytes and B lymphocytes remain, remembering how to fight the disease in future. However, producing T and B lymphocytes after vaccination typically takes several weeks. A person infected just before or just after vaccination may therefore develop symptoms and become ill because the vaccine has not had enough time to provide protection.

What are the types of macrophages?

Macrophages take different forms depending on their tissue, such as histiocytes, Kupffer cells, alveolar macrophages, microglia and others. All, however, are part of the mononuclear phagocyte system. Besides phagocytosis, they play an important role in nonspecific defense (innate immunity) and help initiate specific defense mechanisms (adaptive immunity) by involving other immune cells such as lymphocytes. For example, they present antigens to T cells .

Many macrophage-related diseases have also been identified. In humans, for example, dysfunctional macrophages cause serious diseases such as chronic granulomatous disease, which leads to frequent infections.

In the figure above, a macrophage (large orange cell) is illustrated attacking and destroying bacteria (small green cells).

In the formation of the tumor environment, and when cancer cells metastasize , in the tissues to which they spread there are cells forming the tumor microenvironment , which help cancer cells survive.

Macrophages are the most abundant cells in the tumor microenvironment

Macrophages associated with cancer development and found in the tumor microenvironment are called TİM (tumor-associated macrophages, TAM).

TİMsurvive through GM-CSF signals produced in the tumor environment. CSF1 signals are produced by tumor cells and trigger TİM. In response to this stimulation, TİMalso initiate the signal helping tumor cells metastasize, EGF . In addition to EGF, they secrete VEGF and Wnt7β signals, triggering new blood vessel formationin their surroundings.

In addition, when macrophages lack the anti-inflammatory transcription factor Stat3, a chronic inflammatory response occurs, which triggers adenocarcinoma development in various organs, such as the large intestine.

Macrophages are also very important targets for innovative oncological treatments. As a treatment target, macrophage CSF1 receptorsare blocked using antibodies and small-molecule drugs in an effort to shrink tumors.