Cancer-induced defective cytotoxic T lymphocyte effector function: Anothermechanism how antigenic tumors escape immune-mediated killing

Background: The notion that a deficit in immune cell functions permits tumo r growth has received experimental support with the discovery of several di fferent biochemical defects in T lymphocytes that infiltrate cancers. Decre ased levels of enzymes involved with T-cell signal transduction have been r eported by several laboratories, suggesting that tumors or host cells recru ited to the tumor site actively down-regulate antitumor T-cell immune respo nse. This permits tumor escape from immune-mediated killing. The possibilit y that defects in T-cell signal transduction can be reversed, which would p otentially permit successful vaccination or adoptive immunotherapy, motivat es renewed interest in the field. Summarizing the literature concerning tum or-induced T-cell dysfunction, we focus on the end stage of immune response to human cancer, that of defective cytotoxic T lymphocyte killing function . Based on the data from several laboratories, we hypothesize a biochemical mechanism that accounts for the unusual phenotype of antitumor T-cell accu mulation in tumors, but with defective killing function.