How Do Macrophages Serve as Guardians of Human Body

  • Monocytes, as the largest blood cells in the blood, can still increase to become macrophages when they run away from the blood, and macrophages become guardians of human body.

     

     

    Monocytes are the largest blood cells in the blood, but when monocytes run away from the blood and enter other body tissues, their size will gradually increase, and become macrophages, guardians of human body. The diversity of tissue distribution and heterogeneity of macrophage have made it a popular research object for scientific researchers.

    The Origin of Macrophages

    The evolution of species diversity and the struggle for survival have produced a complex host defense system, which relies on natural immunity. The first explanation of innate immunity was at the end of the 19th century, when Elie Metchnikoff introduced the term "macrophage", in which macro means big, and phage means eater.

    Recent research shows that most macrophages in adult tissues are sown before birth and are extracted from the yolk sac during embryonic development. They have the ability to self-renew and maintain independently of monocytes.

    The Role of Macrophages

    Macrophages are an important component of the human immune system. They can swallow and kill intracellular parasites, bacteria, tumor cells, as well as their own aging and abnormal cells. They play the role of warriors, and can also act like sentinels by reminding other immune cells to "prepare to fight against an enemy invasion". They are of great importance in human body's immune defense, immune stability and immune surveillance. For example, macrophages swallow the fine dust that enters the lungs. It is precisely because of the hard work of macrophages that our lungs are not contaminated by countless dust.

    With the deepening of research, scientists have discovered that it can also regulate organ development, maintain tissue cell homeostasis, affect tissue regeneration, participate in nervous system repair, and so on. The dysfunction of macrophages is closely related to many diseases such as cancer, diabetes and Alzheimer's disease.

    Medical Research Based on Macrophages

    The focus of immuno-oncology has focused on T cells for a long time. In recent years, CTLA4 antibodies, PD-1/PD-L1 antibodies, chimeric antigen receptor (CAR) -T therapy and T cell receptor (TCR) -T therapy have given researchers confidence in curing cancer, and these are all related to T cells. “However, due to the limitations of the characteristics of T-cells, they showed weak performance in solid tumors. So immunotherapy urgently needs new development directions, and the research progress of macrophages has opened another window for immunotherapy.” said a scientist at Creative Biolabs, who focuses on CAR technology.

    The paper published in Science Advances on April 29, 2020, titled Cellular backpacks for macrophage immunotherapy, demonstrates the construction of a "backpack" for macrophages to secrete cytokines so that they can remain in a tumor-killing state for up to 5 days, and it was found that this can delay tumor growth and reduce metastasis in a mouse model of aggressive breast cancer.

    In addition, another paper, Human chimeric antigen receptor macrophages for cancer immunotherapy, published in Nature Biotechnology on March 23, 2020, studied the CAR-Macrophages obtained by genetically modifying macrophages, which may become effective treatments for solid tumors. The genetically modified macrophages not only express the CAR targeting the HER2 antigen, and can specifically phagocytize and eliminate cancer cells in in vitro experiments. Besides, they are also activated to differentiate into a highly pro-inflammatory cell type—M1 macrophages, which secrete pro-inflammatory cytokines, change the tumor microenvironment and stimulate other immune cells such as T cells to participate in tumor killing.

    Advances in science and technology have allowed researchers to see different subpopulations of macrophages with multiple complex biological functions in different tumor microenvironments, and also have a deep understanding of the relationship between macrophages and tumor immunotherapy. Updating the understanding of the biological characteristics of macrophages has become particularly important. In order to deal with various malignant tumors, more treatment strategies combined with macrophages need to be explored in the future.