Klaus Elgert, professor of biology at Virginia Tech, is doing research to determine how cancer interacts with the immune system, particularly with macrophages (Mfs). Mfs are cells in the immune system that digest intruders, or antigens, then display the digested components to other immune cells to elicit their help.
Cancer cells sabotage the ability of Mfs to communicate with other cells of the immune system. Elgert and his colleagues, including his graduate students, have discovered that cancer cells can manipulate gene expression in Mfs through chemical signals so that Mfs do not suppress tumor growth (in fact, tumors can even cause Mfs to promote tumor growth). They are doing research to determine how to return the Mf to its normal activity, to enhance the immune system's ability to fight cancer, and to find other chemicals to kill cancer cells.
Elgert explains that cancer is the "uncontrolled growth of tumor cells, loss of immune surveillance, and destruction of aberrant cells. The cause of this loss of control is varied and differs among different types of tumors."
The long-term objective of research in his lab is to understand the cellular and molecular events involved in tumor-induced immune suppression by Mfs. "We have documented that tumor growth is associated with a decrease in immune function caused by a reduction of positive regulatory factors and an increase in negative regulatory factors," he reports.
The cause of this altered regulatory network is two-fold:
1) the tumor itself releases negative factors when some cancer cells mimic immune-system cells; and
2) the immune cells are altered, especially Mfs, so that they join the cancer cells in turning down the immune system.
Recently, it was discovered that Mfs help regulate infections and tumors through the production of interleukin (IL)-12, a vital communication molecule between Mfs and other immune cells. What if Mfs don't produce enough IL-12? Elgert's research has demonstrated that Mfs in animals with tumors make less IL-12.
In addition, the researchers have discovered that the impact is not just limited to the tumor, but the immune system throughout the body is compromised, Elgert says.
To combat this loss of immune function, Virginia Tech's immunologists are investigating two possible therapeutic agents that have been documented to stimulate the immune response: paclitaxel (taxol) and IL-12.
It has long been recognized that taxol disables cancer cells - particularly in the cancers that affect women's reproductive systems. The discovery that taxol also stimulates Mfs to produce IL-12 is relatively new.
The researchers are examining how taxol boosts Mf function, determining how tumor growth alters IL-12 regulation, and examining the effectiveness of taxol and IL-12 in compensating for the documented loss of immune system function using a novel combined gene therapy and chemotherapy approach.
"Determining how tumor growth changes the delicate and complex checks and balances that regulate the immune response is leading not only into an appreciation of the abnormalities of immune functions, but normal immunity. Eventually it may be possible to treat diseases such as cancer by selectively stimulating under-active parts of the immune system and by reducing the tumor's ability to suppress immune responses," says Elgert.
He proposes that scientists may someday be able to engineer cells to produce IL-12, then inoculate the site of the tumor with these cells, which will undergo a limited number of cell replications and then die. This IL-12 will augment immune activity local to the tumor.
Within 10 years, it is likely that the human genome will be mapped and there will be a catalog of normal genes. "The next step will be to learn how to introduce normal genes to replace or inactivate abnormal genes, to provide genes when they are missing, or to turn-on inactive genes. For example, can the ability to produce IL-12 be turned on if cancer has turned it off?" asks Elgert.
Link to more information about immunology research.