A novel immunotherapeutic modality with direct hemoperfusion targeting transforming growth factor-β prolongs the survival of tumor-bearing rats

Abstract

Immune responses are frequently depressed in patients with cancer. One of the reasons for a poor immune response is the presence of increased levels of immunosuppressive substances associated with tumor growth. Transforming growth factor-beta (TGF-beta), a representative immunosuppressive cytokine, plays various roles in the progression of cancer. To remove immunosuppressive substances from tumor-bearing hosts, we developed an immunosuppressive substance adsorption (ISA) column for direct hemoperfusion (DHP) treatment. It is filled with extra-fine fibers that can adsorb TGF-beta. In this study, we investigated the effects of this DHP treatment on serum levels and activities of TGF-beta, cellular immune responses, and anti-tumor effects in KDH-8 (TGF-beta-producing hepatocellular carcinoma cell line)-bearing rats. We further studied the ability of ISA fibers to adsorb tumor-associated immunosuppressive cytokines [TGF-beta, interleukin (IL)-6 and vascular endothelial growth factor (VEGF)] in samples of body fluids obtained from patients with metastatic cancer. DHP treatment decreased serum levels and activities of TGF-beta in tumor-bearing rats and restored T lymphocyte response to mitogen. Tumor growth in rats treated by DHP was significantly slower than that in untreated rats. The survival time of treated rats was significantly longer than that of untreated rats. The concentrations of TGF-beta, IL-6, and VEGF in the samples of human body fluids were decreased markedly by in vitro treatment with ISA fibers. These results suggest that DHP treatment with an ISA column, which removes TGF-beta and other immunosuppressive substances from the sera of tumor-bearing hosts, is potentially a new immunotherapeutic strategy for cancer.