Manipulating the Immune System to Defeat Cancer

immuneIn 2015 5.6 billion dollars was spent towards cancer research. In this same year, 7.6 million people died from cancer. Top researchers in vast science fields are expanding theories and approachs to defeating cancer. Our immune system destroys 10,000 cancer cells a day, but the multiplication of each cell becomes uncontrollable for the human immune system. If only we could alter our immune system to create the perfect defense, As if cancer could be handled in any severity. This theory is called “immunoediting”

The human immune system goes through three phases when encountering cancer. These ohases are called Elimination, Equilibrium, and Escape. Eliminating phase is the intial response to the recognition of cancerous cell. Immune effector T cells, B cells, and Natural Killer (NK) cells are the first line of defense, which will then call upon an adaptation for further destruction. Cytokine Interferon Y (IFN-y) is then released to prevents replication of infected cells. This response isn’t a success over the capabilities of the tumor’s immune shutdown, but it has been recognized as the basis to our immune response to cancer. Evidence of a intial strong immune response has been shown through a negative outcome called Paraneoplastic disease. This disease causes a patient to suffer from nervous system mountfunctioning from an effecient cancer antibody immune response. Paraneoplastic disease is studied to unlock what causes such an efficient attack towards cancer cells. In equilibrium phase the immune system is balanced out by the Tumor growth. T cells such as CD4+ and CD8+ create an abnormal development of the tumor’s size and shape, but not restricting the growth in all. The final phase Escape, the tumor disables the immune system’s reproduction, development, recognition, and response. An Enyzyme Indolamine 2 3-Dioxygenase (IDO) produced by tumors causes T cells to go through apoptosis (programmed cell death) and lowers the production of T cells. This happens because IDO controls the rate of the amino acid Tryptophan, an essential building block for protiens. The definciency of these protiens causes the immune system to become even less effective against the rapid growth of cancerous cells. Myleoid cells are young white blood cells in bone marrow. White blood cells is the immune systems general cell defense against virus’s and diseases’s . Tumors will mutate myeloid cells circulating through the body into a myeloid-derived suppressor cell (MDSCs). Suppressor cells shut down the immune response when a disease or virus is defeated. It is expressed by NOS2 and ARG1 in which it destroys anti tumor T cells. Tumor associated macrophages (TAMs), stimulates the growth of blood vessels and inflammation of the tumor. Blood vessels create structure for vessel formation in a tumor. By knowing the expressing enzymes NOS2 and ARG1 researches are in the process of preventing MDSCs and TAMs. Tregs is a immunosupressor of APCs, T cells, B cells, NKT cells, and NK cells of the thymus, a T cell production organ located behind the sternum. The cancerous tumor uses Tregs, TAMs, and MDSCs to shutdown the immune system.

Inflammation is a direct association with cancer. Disruptions of transciption factor NK-kB directly promotes inflamation and malignant cell replication. Malignant Cells is reffereed to the progress of cancer cells often resulting in death of the organism it’s infecting. Pattern recognition receptors (PRR) recognize pathogines for the immune system to destroy. Our immune system however often fails in this response leading to inflimation. TNF-a a protien involved in inflimation induces NF-kB to cause a resistence of apoptosis and promote cell replication which enhance angiogensis (vessel production) and disrupt immune survellience in favor of the tumor, this is called TRAIL. IL-6 an inflamation promoter secreted by T cells has been proven to cause Multiple myeloma a white blood cell cancer. Our immune system has created malignant cells with pathways IL-6, TNF-a, and PRR. Protiens secreted by the immune system IL-10 and TGF-B have prooved to supress the inflammator and immune microenvironment created by the tumor. The tumor reacts to this with STAT3, IL-10, IL-6, and VEGF, enhancing the malignant growth, inflammation, and micro tumor immune system. T cells, NK cells, and macrophages are yet again supressed. Tumors create a micro environment completely unvolnerable to our immune system by manipulation.

Vaccine TLR agonists a vaccine which contains CpG dinucleotides (CpG ODN) activates a pathogen receptor prooven to stimulate antitumor immunity. CpG ODN is used inĀ hepatitisĀ B and influenza vaccine. This vaccine is being tested for after chemotherapy immune system boost. Dendritic cells (DC) are indirectly activated by TLR agonist and work as antigen identifier. If a DC vaccine were injected near a tumor, this would create a tumor specific immune response for T cells and B cells. The immune receptor vaccinations would increase the response and adaptations necessary to destroy cancer. Immunologists are targeting the specific antigens of tumors. This would point towards which T cells are active during the response to cancer. Manifacturing and injecting these T cells is a immunotherapy in stimulating our defense. T cell immunotherapy would extend to a T cell memory vaccine for the destruction of a cancer no matter what stage of development.