Tumor Antigens

Tumor Antigens

Tumor cells also express unique molecules that can be classi-fied into two groups:

i.               Tumor-specific antigens

ii.               Tumor-associated transplantation antigens

◗ Tumor-specific antigens

The tumor-specific antigens (TSAs), also called tumor-specific transplantation antigens, are unique to tumors. They are not found on other cells of the body. They are usually the products of mutated genes seen in the cancer cells. Cytosolic processing of the abnormal proteins yields peptides that are unique and when presented by the appropriate MHC class I molecules elicit a cell-mediated immune response.

Various physical and chemical carcinogens cause malignan-cies by inducing mutation in key genes involved in modulating cell growth. Ras proto-oncogene products including the p21 Ras pro-teins and other related gene products are an example of TSAs. Ras proteins bind guanine nucleotides (GTP and GDP) and possess intrinsic GTPase activity. The mutations associated with Ras genes in malignant cells appear to cause a single amino acid substitu-tions at specific positions (12, 13, or 61), which results in increased enzymatic activity of the gene product. As a consequence, the cells acquire transforming capacity. Moreover, these products are also recognized as foreign antigens by the cellular immune response.

Another mode through which the tumor cells may express unique and novel antigens “is by” integration with proviral genomes. These virus-induced tumors usually have their genome integrated with proviral genome, hence the proteins encoded and expressed are sometimes novel and recognized by the cellular immune response. Viruses that have been implicated in tumorigenesis include Epstein–Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), etc.

◗ Tumor-associated transplantation antigens

Tumor-associated transplantation antigens (TATAs) are the other class of tumor antigens. These antigens are expressed by (a) tumor cells and also by (b) normal cells at low levels or only dur-ing the process of differentiation. The expression of these anti-gens is considerably derepressed or enhanced after the process of malignant transformation. TATAs can be of the following types:

1. Tumor-associated carbohydrate antigens: They representabnormal form of mucin-associated antigen detected in breast and pancreatic cancers.

2. Differential antigens: These include CD10 and prostate-specific antigens (PSA). The latter is used as a diagnostic indica-tor in prostatic cancer.

3. Oncofetal antigens: These antigens are found in embryonicand malignant cells but are absent in normal adult cells. Alpha-fetoprotein and carcinoembryonic antigens are examples of this antigen, which are found in hepatomas and colonic cancers, respectively. Silent tumor-associated genes are not expressed in normal cells but are actively transcribed in tumor cells. Tissue-specific genes or differentiation genes are present in the surface of normal cells or may be shed to the circulation, but the levels of expression are usually very low in normal cells. This finds practi-cal application in the diagnosis of malignancies as illustrated by the assay of PSA for the diagnosis of carcinoma of prostate.

PSA: It is a kallikrein-like serine protease produced exclusively bythe epithelial cells in the prostate gland. The antigen is detectable at relatively high levels in seminal plasma and at very low levels in the serum of healthy men. The assay of serum PSA levels is a very useful marker of prostate carcinoma, perhaps the most meaning-ful serum marker for neoplasia. In healthy men, the levels of PSA vary between 0.65 0.66 ng/mL at ages 21–30 and 1.15 0.68 ng/mL at ages 61–70. Significantly elevated levels are demon-strated in 63–86% of patients with prostatic carcinoma, depend-ing on the stage. In essence, antigens of tumors that are capable of eliciting an immune response may be one of the following nature:

·           First, these antigens are uniquely expressed by tumor cells alone. Also, there are the products of genes that have been mutated during the process of transformation, leading to the expression of abnormal products.

·           Second, certain antigens expressed by tumors are present only when normal cells are undergoing the process of dif-ferentiation and these are also readily recognized by the immune system.

·           Finally, the antigens that are overexpressed by the tumor cells elicit a good immune response.