One of the key functions of the immune system is to patrol the body for cancer cells in order to kill these cells before they become malignant tumors. In this chapter we will discuss (1) how the immune system is able to recognize cancer cells; (2) how cancer cells evolve to hide from and suppress the immune system; and (3) how recent advances in immunotherapy overcome these strategies to re-invigorate the immune system’s killing mechanisms.
Malignant cancer cells are genetically similar to healthy cells. They generally display the same major (HLA) and minor histocompatibility proteins as other nucleated “self” cells, and lymphocytes with antigen receptors that could recognize these proteins are largely removed during negative selection (see Chapter 66). Nevertheless, animals carrying a malignant tumor can develop an immune response to that tumor and cause its regression. In the course of neoplastic transformation, new antigens (neoantigens), called tumor-associated antigens (TAAs), develop at the cell surface, and the host recognizes such cells as “nonself.” An immune response then kills the offending cells, preventing the formation of a malignant cancer.
TAAs can either be highly specific (i.e., cells of one tumor will have different TAAs from the cells of another tumor) or be shared by different tumors, even tumors that occur in different hosts. For example, virus-induced tumors (such as those due to human papillomavirus) tend to have TAAs that cross-react with one another if induced by the same virus strain. This feature has spurred interest in developing antitumor vaccines that use the shared, virus-induced TAAs found in all individuals who have that virus-induced tumor.
CARCINOEMBRYONIC ANTIGEN & ALPHA-FETOPROTEIN
Some human tumors contain antigens that normally occur in fetal but not in adult human cells.
Carcinoembryonic antigen circulates at elevated levels in the serum of many patients with carcinoma of the colon, pancreas, breast, or liver. It is found in fetal gut, liver, and pancreas and in very small amounts in normal sera. Detection of this antigen can be helpful in the diagnosis of such tumors, and if the level declines after surgery, it suggests that the tumor is not spreading. Conversely, a rise in the level of carcinoembryonic antigen in patients with resected carcinoma of the colon suggests recurrence or spread of the tumor.
Alpha-fetoprotein is present at elevated levels in the sera of patients with hepatocellular cancer and is used as a marker for this disease. It is produced by fetal liver and is found in small amounts in some normal sera. However, it is nonspecific; it occurs in several other malignant and nonmalignant diseases.
Monoclonal antibodies directed against new surface antigens on malignant cells (e.g., B-cell lymphomas) can be useful in diagnosis. Monoclonal antibodies coupled to toxins, such as diphtheria toxin or ricin, a product of the Ricinus plant, can kill tumor cells in vitro and someday ...