Tumor antigen is anantigenic substance produced intumorcells, i.e., it triggers animmune response in thehost. Tumor antigens are usefultumor markers in identifying tumor cells withdiagnostic tests and are potential candidates for use incancer therapy. The field ofcancer immunology studies such topics.
Normalproteins in the body are not antigenic because ofself-tolerance, a process in which self-reacting cytotoxicT lymphocytes (CTLs) andautoantibody-producingB lymphocytes are culled "centrally" in primary lymphatic tissue (BM) and "peripherally" in secondary lymphatic tissue (mostlythymus for T-cells andspleen/lymph nodes for B cells). Thus any protein that is not exposed to theimmune system triggers an immune response. This may include normal proteins that are well sequestered from the immune system, proteins that are normally produced in extremely small quantities, proteins that are normally produced only in certain stages of development, or proteins whose structure is modified due to mutation.
Initially tumor antigens were broadly classified into two categories based on their pattern of expression:Tumor-Specific Antigens (TSA), which are present only on tumor cells and not on any other cell andTumor-Associated Antigens (TAA), which are present on some tumor cells and also some normal cells.
This classification, however, is imperfect because many antigens thought to betumor-specific turned out to be expressed on some normal cells as well. The modern classification of tumor antigens is based on their molecular structure and source.
Accordingly, they can be classified as;[citation needed]
Any protein produced in a tumor cell that has an abnormal structure due tomutation can act as a tumor antigen. Such abnormal proteins are produced due to mutation of the concernedgene. Mutation ofprotooncogenes andtumor suppressors which lead to abnormal protein production are the cause of the tumor and thus such abnormal proteins are calledtumor-specific antigens. Examples of tumor-specific antigens include the abnormal products ofras andp53 genes. In contrast, mutation of other genes unrelated to the tumor formation may lead to synthesis of abnormal proteins which are calledtumor-associated antigens.
Other examples include tissue differentiation antigens, mutant protein antigens, oncogenicviral antigens,cancer-testis antigens and vascular or stromal specific antigens. Tissue differentiation antigens are those that are specific to a certain type of tissue. Mutant protein antigens are likely to be much more specific to cancer cells because normal cells shouldn't contain these proteins. Normal cells will display the normal protein antigen on their MHC molecules, whereas cancer cells will display the mutant version. Some viral proteins are implicated in forming cancer (oncogenesis), and some viral antigens are also cancer antigens.Cancer-testis antigens are antigens expressed primarily in thegerm cells of thetestes, but also in fetalovaries and thetrophoblast. Some cancer cells aberrantly express these proteins and therefore present these antigens, allowing attack by T-cells specific to these antigens. Example antigens of this type areCTAG1B andMAGEA1.[1]
Proteins that are normally produced in very low quantities but whose production is dramatically increased in tumor cells, trigger an immune response. An example of such a protein is theenzymetyrosinase, which is required formelanin production. Normally tyrosinase is produced in minute quantities but its levels are very much elevated inmelanoma cells.
Oncofetal antigens are another important class of tumor antigens. Examples arealphafetoprotein (AFP) andcarcinoembryonic antigen (CEA). These proteins are normally produced in the early stages of embryonic development and disappear by the time the immune system is fully developed. Thus self-tolerance does not develop against these antigens.
Abnormal proteins are also produced by cells infected withoncoviruses, e.g.EBV andHPV. Cells infected by these viruses contain latent viralDNA which istranscribed and the resulting protein produces an immune response.
In addition to proteins, other substances like cell surfaceglycolipids andglycoproteins may also have an abnormal structure in tumor cells and could thus be targets of the immune system.
Tumor antigens, because of their relative abundance in tumor cells are useful in identifying specific tumor cells. Certain tumors have certain tumor antigens in abundance.
| Tumor antigen | Tumor in which it is found | Remarks |
|---|---|---|
| Alphafetoprotein (AFP) | Germ cell tumors | |
| Carcinoembryonic antigen (CEA) | Bowel cancers | Occasional lung or breast cancer |
| CA-125 | Ovarian cancer | |
| MUC-1 | Breast cancer | |
| Epithelial tumor antigen (ETA) | Breast cancer | |
| Tyrosinase | Malignant melanoma | normally present in minute quantities; greatly elevated levels in melanoma |
| Melanoma-associated antigen (MAGE) | Malignant melanoma | Also normally present in thetestis |
| abnormal products ofras,p53 | Various tumors |
Certain tumor antigens are thus used astumor markers. More importantly, tumor antigens can be used in cancer therapy astumor antigen vaccines.[2]
