Tumor-induced Immunosuppression

Aging

Investigators

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Abstract

We initially observed, and it has been widely reproduced, that T cells from tumor-bearing hosts are defective in their signalling in response to antigen and in their function. A variety of defects are noted including defective nuclear translocation of the p65 NF-kappa B transcription factor, shortened half-lives for a number of cellular proteins such as TCR-zeta chain and signalling kinases of the src family, among others, and a deviation of the cytokine production profile toward Th2 cytokines (IL-4, IL-10) and away from Th1 cytokines (interferon- gamma, TNF). Evidence of suppression of immune function in mice in whom tumor is growing in hollow fibers in the peritoneal cavity without any cell-cell contact in the host suggest that a soluble tumor factor is responsible for the defect in cellular immunity. We have devised a method of reproducing these tumor- induced changes in normal T cells in vitro and are in the process of isolating the tumor-derived factor(s) responsible for the changes. In agreement with this finding, we are able to demonstrate the immunosuppressive properties of the pleural fluid isolated from cancer patients. We are in the process of isolating and characterizing the tumor-derived factor(s) from the pleural fluids of cancer patients.