Phases of Immunoediting

The study of the relationship and interactions between the immune system and cancer or malignant cells is known as cancer immunology.

A malignancy refers to cancerous cells that have the potential to invade and destroy tissue. The growth of malignant cells is often fast and uncontrolled due to the changes in their genetic makeup. [2]

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The body monitors, detects and destroys malignant cells through a process called immunosurveillance. Immunosurveillance can be used by the immune system to detect any early warning signs of possible damaged cells such as cancer, before they are able to develop further. [3] It is also able to inhibit carcinogenesis and help maintain normal cellular homeostasis. However it is believed that immunosurveillance is only a more general process of cancer immunoediting. [4]

Immunoediting is a process where the body is protected from cancer cell growth and the development of tumour immunogenicity by the immune system. It consists of three main phases, elimination, equilibrium and escape, also known as the three E’s. [5]

Elimination phase:

• Phase 1: Begins with the initiation of an antitumor immune response, in which the immune system is able to recognise the presence of a developing tumor that has undergone stromal remodelling which is causing damage to the tissue. The inflammatory process is activated resulting in the recruitment of natural killer cells, natural killer T cells, macrophages and dendritic cells to the site of the tumor. The natural killer cells and the natural killer T cells are then stimulated to produce IFN-gamma.
• Phase 2: Newly synthesised IFN-gamma causes partial cell lysis of the tumor as well as initiating the production of chemokines. The role of the chemokines is to inhibit the formation of new blood vessels. The debris from the cell lysis of the tumor is then engulfed by dendritic cells and the dendritic cell migrates to the lymph nodes.
• Phase 3: Natural killer cells and macrophages transactivate each other due to the presence of IFN-gamma. This then results in apoptosis of the tumor. The dendritic cells in the lymph nodes activate the differentiation of Th1 cells which then results in the development of CD8 T cells.
• Phase 4: Tumor specific CD4 and CD8 cells as well as cytolytic T lymphocytes then destroy any remaining antigen-bearing tumor cells. If some of the tumor cells remain and haven’t been killed off in the elimination phase, then the second phase of immunoediting occurs. [6]

Equilibrium Phase:

Tumor cells that have survived enter the equilibrium phase. Lymphocytes and IFN-gamma exert a certain amount of pressure on to the tumor cells which are genitically unstable and rapidly mutating. [6]

Escape phase:

Tumor cells then enter the escape phase due to the fact that they have built up resistance to elimination. Tumor cells grow and expanded uncontrollably which can result in malignancies. [6] This occurs due to the balance between the immune system and the tumor to be disturbed resulting in the tumor taking over. There is rapid tumor growth due to immune exhaustion or inhibition due to the tumor being resistant to the immune systems efforts to kill it.[7]

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A Diagram to illustrate immunoediting:

To conclude, I do believe that there is a link between the immune system and the development of a malignancy. Tumor infiltration by lymphocytes is seen as a reflection of a tumor-related immune response[6].

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