The role of therapeutic apheresis in the treatment of cancer: a review

Abstract

Immunosuppression is a hallmark of advanced malignancies in man. Over the past 40 years, many investigators have identified soluble immunosuppressive factors in blood, serum, ascitic fluid, and pleural fluid from cancers in man and other species. Suppressive factors have also been identified that are produced by tumors. The description of immunosuppressive factors in the blood of vertebrates who either have cancer or who are pregnant is significant, for only in pregnancy and cancer does a seemingly normal immune system tolerate immunogenic neoantigen. Tumor necrosis factors (TNFs) are known to be pleiotropic cytotoxic cytokines that are produced by macrophages and lymphocytes. These cells are thought to be suppressed in patients who have cancer or who are pregnant. Recently, elevated blood levels of soluble tumor necrosis factor receptors (sTNFRs) have been reported in the blood in a variety of cancers and pregnancy. In 1990, after our initial publication of the discovery of sTNFRs in the serum and low molecular weight ultrafiltrates of serum from a variety of cancer patients, others confirmed significant elevations of sTNFRs in cancer patients. This elevation was found to correlate with a poor prognosis. The biologic activity of proinflammatory cytokines as well as the suppressive role of their shed receptors is herein reviewed. Work with cancer patients using ultrapheresis to reduce these suppressive molecules by the authors and others is reviewed. Several recommendations are made for future directions.