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Immunogenicity and Genetic Mechanisms
This Sqadia lecture elucidates how the immunity of tumor works. Immunogenicity is an ability of a tumor to induce an immune response (mostly mediated by T cells) that can prevent its growth. Paul Ehrlich: The immune system has the ability to repress cancer growth. Burnet: Tumors express neo-antigens that induce immune responses that are capable of eliminating developing tumors. Lewis: Organisms have well-developed mechanisms that are similar to graft rejection mechanisms that protect against cancer formation. These theories led to the concepts of cancer immuneosurveillance or immunoediting. Immunoediting is a process by which a person is protected from cancer growth and the development of tumor immunogenicity by their immune system/ lymphocytes. Tumor cells continue to grow and expand in an uncontrolled manner and may eventually lead to malignancies. Members of the melanoma antigen (MAGE) A, B or C families and LAGE families, encode tumor-specific antigens in many types of tumor cells.
Failure of Tumor Growth Control
Weak immunogenicity is the root cause of why the immune system ultimately fails to control tumor growth. Resistance render tumor cells less sensitive to immune attack. Tumors develop a plethora of immunosuppressive mechanisms early in tumor development and when immunosuppression fails, resistant variants emerge. The local tumor immune response becomes increasingly compromised, reduced effector functions and limited persistence. Failure of the immune response to control tumor progression. Immunosuppression is an inhibition of anti-tumor immune responses directly or induce other cells to do so. Direct inhibition is an expression of programmed cell death protein ligands. In direct inhibition is an induction through regulatory T cells. Two major criteria/ requirements that dictate tumor immunogenicity are:
•Adequate levels of uniquely expressed antigens
•Tumor cells effectively present antigens in a form that leads to immune activation instead of immune tolerance
General Features of Tumor Immunity and Tumor Antigens
Tumors express antigens that are recognized as foreign by the immune system of the tumor-bearing host. Immune responses frequently fail to prevent the growth of tumors. The immune system can be activated by external stimuli to effectively kill tumor cell and eradicate tumors. Rapid tumor growth overshadows immune system capacity to eradicate tumors. Different tumors have different responses to evade immunity.
Immune Response to Tumors and their Immune Evasion
The innate immune response to tumors and its role in the induction of T-cell immunity. Natural killer (NK) cells recognize many tumor cells but not normal self-cells, and they are thought to aid in the elimination of nascent tumors. Two main strategies are employed by NK cells to recognize tumor targets. Tumor-associated antigens (TAAs) are one of the fundamental triggers of the immune response. They are important because they activate, via, major histocompatibility complex (MHC), the T cell response, an important line of defense against tumorigenesis. Immunoediting is a dynamic process that consists of immuneosurveillance and tumor progression. It describes the relation between the tumor cells and the immune system. It is made up of three phases: elimination, equilibrium, and escape.
Immunotherapy for Tumors
Immunotherapy, also called biologic therapy, is a type of cancer treatment that boosts the body's natural defense to fight the cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function. Immunotherapy may work in these ways:
•Stopping or slowing the growth of cancer cells
•Stopping cancer from spreading to other parts of the body
•Helping the immune system work better at destroying cancer cells
There are several types of immunotherapy, including:
•Oncolytic virus therapy