Abnormal Cell Growth

SCENARIO 5 Abnormal cell growth SCENARIO Normal cells can change their characteristics and develop into benign and malignant neoplasms due to various factors. The body's immune system will respond and inhibit the development of abnormal cells. The ability of cells to evade the immune system, initiate an inflammatory response, avoid cell death, and increase proliferation signals causes malignant neoplasm cells to continue to grow. What is the initial immune mechanism to respond to cancer cells or neoplasm cells? For more than a century it has been discovered that the physiological function of the adaptive immune system is to prevent the growth of transformed cells and to destroy these cells before they become dangerous tumors.The control and elimination of malignant cells by the immune system is called immune surveillance. Several lines of evidence support the idea that immune surveillance of tumors is important for preventing tumor growth. However, the fact that common malignant tumors develop in immunocompetent individuals suggests that tumor immunity is often unable to prevent tumor growth or is easily defeated by rapidly growing tumors. In addition, one of the characteristics of cancer is its ability to evade damage by the immune system. This leads to the conclusion that the immune response to tumors is often dominated by tolerance or regulation, not by effective immunity. The field of tumor immunology has focused on defining the types of tumor antigens to which the immune system reacts and the nature of the immune response, and developing strategies to maximally enhance antitumor immunity. Tumor Antigen Malignant tumors express various types of molecules that can be recognized by the immune system as foreign antigens. If the immune system is capable of reacting to a tumor in an individual, the tumor must express an antigen that is seen as nonself by the individual's immune system. Common tumor antigens can be classified into several groups: • The product of various mutated genes. Recent tumor genome sequencing has revealed that common human tumors harbor a large number of mutations in diverse genes, which do not play a role in tumorigenesis and are called passenger mutations. The products of many of these altered genes can stimulate adaptive immune responses in tumor patients. In experimental tumors induced by chemical carcinogens or radiation, tumor antigens are also mutants of normal cellular proteins. Almost all genes can undergo random mutagenization in different tumors. • The product of a mutated oncogene or tumor suppressor gene. Some tumor antigens are the products of mutated or translocated oncogenes or tumor suppressor genessuspected to be involved in the process of malignant transformation, called driver mutations. This type of mutation can encode a protein that is considered foreign. New proteins produced across translocation breakpoints may also function as tumor antigens. • Aberrantly expressed proteins. In some human tumors, the antigens that elicit an immune response appear to be normal (non-mutated) proteins whose expression is not regulated in the tumor. These structurally normal self antigens are not expected to elicit an immune response, but their aberrant expression may be sufficient to make them immunogenic. For example, self proteins expressed only in embryonic tissues may not induce tolerance in adults; thus, the same protein expressed in the tumor may be recognized as foreign by the immune system. • Viral antigens. In tumors caused by oncogenic viruses, the tumor antigen may be a product of the virus.