Immunoediting is a theory that describes the transformation of normal cells to clinically-detectable cancer. The theory implies that while the human immune system protects from cancer, it also drives the development of tumors that will undergo immunogenic “sculpting” and may survive immune cell attacks. Proposed by Gavin P. Dunn, MD, PhD, and Robert Schreiber, PhD, the immunoediting process consists of three phases, often referred to as the “3 Es”: elimination, equilibrium and escape [Three Phases of the Cancer Immunoediting Process].
Three Phases of the Cancer Immunoediting Process
Source: Smyth MJ, et al. Adv Immunol. 2006;doi:10.1016/S0065-2776(06)90001-7.
Both innate and adaptive immune cells play a role in immune surveillance. In this phase, growing tumors are completely eliminated by the immune system.
Some cancer cells may not be controlled by the innate and adaptive immune cells during elimination. When this occurs, the cells able to survive elimination replicate with new variants that may be more resistant to the immune response. During this phase, cancer remains clinically undetectable and is dormant. Patients whose tumors are in equilibrium may either revert to elimination or progress on to the escape phase.
In this phase, cancer cells have escaped the immune system and are replicated, leading to clinically detectable tumors. Immune escape can be facilitated through various mechanisms: the immune system may not recognize tumor cells; the cells may become resistant to immune cell attacks; or inflammation and the tumor microenvironment may lead to increased immunosuppression. The tumor microenvironment may contain many (inflamed tumors) or few (non-inflamed tumors) immune cells.
It is well established that the immune system continually scans the body for threats and then, when appropriate, mounts an immune response. This process is known as immune surveillance. The immune surveillance theory is strongly supported by the increased incidence of cancers in immunocompromised individuals. Immune surveillance is the first phase (elimination) of the immunoediting process, outlined by Dunn and Schreiber and described in more detail below.
The basis of the immune surveillance theory is that tumors produce antigens that may evoke an immune response. Tumor-specific antigens (found exclusively on tumor cells) or tumor-associated antigens (found on both tumor and normal cells but overexpressed on tumor cells) may trigger the immune system response.
When a patient’s immune system is functioning properly and able to mount appropriate responses to antigens, the patient is considered to be immunocompetent. Patients whose immune systems are not able to respond appropriately to antigens are referred to as immunodeficient or immunocompromised. Most often, cancer occurs in those without any obvious immunodeficiency, suggesting that tumor cells have adapted ways to escape immune surveillance.
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