REVERSAL OF TUMOR-INDUCED IMMUNOSUPPRESSION - A NEW APPROACH TO CANCER-THERAPY

Many studies show defective immune responses in patients diagnosed wit h cancer. Most of the diverse nonspecific approaches used to stimulate the immune system to recognize and destroy abnormal tumor cells have limited clinical utility. Attempts to identify tumor-specific antigens and to improve the antigen presentation were equally disappointing. I t appears that some of these failures can be explained by tumor-induce d immunosuppression. A large number of cytokines, hormones, and other molecules secreted by tumors were demonstrated to have immunomodulatin g properties. The most extensively studied immunosuppressive molecules secreted by tumors are transforming growth factor-beta (TGF beta), in terleukin 10 (IL-10), and prostaglandin E-2 (PGE(2)). TGF beta in part icular may play a key role in tumor-induced immunosuppression. It is t he most potent immunosuppressor described to date, and it has been con sistently isolated from variety of tumor cell lines and detected in pl asma of tumor-bearing hosts. Level of TGF beta production by tumor cel ls correlates with their metastatic potential, and TGF beta neutraliza tion not only prevents development of metastases, but also inhibits gr owth or completely eradicates tumors as diverse as breast cancer, mela noma, and malignant gliosarcoma in animal models. PGE, may play signif icant role in early stages of tumor development, promoting the process of tumorigenesis in some tumors. Research on reversal of tumor-induce d immunosuppression promises new, more powerful, and less toxic approa ches to cancer therapy. Existence of molecule(s) consistently secreted by different types of tumors and responsible for tumor progression ra ises the possibility of a single, universal assay to monitor progressi on and recurrence in many malignancies, including those that currently do not have reliable plasma markers.