The Role of Immune System in Tumor Prevention
The immune system has three primary roles in the prevention of tumors. First, the immune system can protect the host from virus-induced tumors by eliminating or suppressing viral infections. Second, the timely eliminate pathogens and prompt resolution of inflammation can prevent the establishment of an inflammatory environment conducive to tumorigenesis. Third, the immune system can specifically identify and eliminate tumor cells on the basis of their expression of tumor-specific antigens or molecules induced by cellular stress. The cancer immune editing theory dipicts the significance of immune system in cancer development and progression. The ultimate goal of cancer treatment is to stimulate the innate immune defense system of patients through tumor antigen proteins and adjuvants, so tumor antigen proteins play a vital role in cancer research. At present, the tumor immunoediting concept is divided into 3 phases, early eliminating stage, equilibrium stage and immune escape stage of tumor cell variation. These three stages can occur in different tumor sites at the same time, but it is not inevitable that tumor cells interact with each other in the immune system. Kinds of proteins in these processes can be used as the tumor biomarker in tumor research applications and Creative BioMart can provides you these molecular tools.
Figure 1. Extrinsic tumor suppression by the immune system. DR5, death receptor 5; IDO, indoleamine 2,3-dioxygenase; MICA/B, MHC class I chain–related antigens A and B; RAE1, retinoic acid early transcript 1; sMICA/B, soluble MICA/B; ULBP, UL16-binding protein. (Jeremy, et al. 2007)
As shown in figure 1, cancer immunoediting is now considered a process composed of 3 phases: elimination; equilibrium and escape, where tumor cells emerge that either display reduced immunogenicities or engage a large number of possible immunosuppressive mechanisms to attenuate antitumor immune responses leading to the appearance of progressively growing tumors. These phases have been termed the 3 Es of cancer immunoediting.
Tumor-specific Antigens (TSAs)
Tumor antigens can be broadly classified as tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs). The former is a new antigen present only on the surface of certain tumor cells. Studies have shown that TSA can induce the body to produce a specific immune response to the tumor, which can clear the tumor or inhibit tumor growth. Back in 1991, scientists confirmed the existence of the first TSA, called Recombinant Human Melanoma-Associated Antigen 1(MAGE-1), and then used MAGE-1 protein as a target for immune attacks against tumors, using a genetic vaccine or a dendritic cell DC vaccine. MAGE-1 protein was used to inhibit tumor growth. Western blot analysis showed that all the three human lung cancer cell lines expressed MAGE-l protein. The expression rate of MAGE-1 protein in NSCLC tissue was 44.6%, indicating that nearly half of NSCLC patients are expected to receive immunotherapy targeting MAGE-1 protein. Moreover, a large number of TSA have been found to play a functional role in the transformed phenotype of tumor cells. The latest study shows that tumor specific growth factor (TSGF) has a definite clinical expression effect in patients with epithelial ovarian cancer. The expression levels of TSGF in serum and tumor tissues in patients with non-small cell lung cancer (NSCLC) were related to postoperative survival.
Tumor-associated Antigens (TAAs)
TAAs are normal cellular proteins that are abnormally expressed in tumor cells. There are a number of different types of TAAs that are categorized based on the normal characteristics of their expression level and location in the body. TAA provides the basis for studying the role of tumor diagnosis and immunotherapy. The carcinoembryonic antigen (CEA) discovered in 1965 belongs to TAA and is an embryogenic carcinogenic antigen. It is considered to be a marker of colon cancer, but further studies have found that it is expressed in various digestive tract tumors. Human epidermal growth factor receptor 2 (Her-2) is one of the most studied TAAs in tumor immunotherapy and has been overexpressed in several human adenocarcinomas. In vitro studies have shown that this CAR-T cell has specific anti-Her-2 (+) Tumor cell action has a significant inhibitory effect on Her-2(+) tumor growth in animal models, and this result brings new hope for the treatment of some Her-2(+) tumor patients. Therefore, the treatment of cancer with tumor antigens has become a hot topic in the medical field.
Categories of Tumor Antigens
By inducing tumor antibodies, antigens expressed on the surface of tumor cells are usually divided into the following categories: 1) testicular cancer antigen, which is expressed only in germ cells and tumor cells, such as MAGE,NY-ESO-1;2) differentiation antigens, expressed only in restricted lineages such as melanocytes, such as collinase, gp100; 3) variant antigen, a structural change of a protein, such as CDK4, p53; 4) magnified antigens, such as overexpression of Her2/neu,p53; 5) antigen splicing variants, such as ING1, NY-CO-37/PDZ45; 6) glycolipid antigens; 7) viral antigens, such as HPV,EBV.
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