Mechanisms of immunologic antitumor therapy: lessons from the laboratory and clinical applications

The use of interleukin 2-based immunotherapies for cancer has been associated with significant resonses in tumor models in both mouse and humans. Further definition of the elements responsible for response is now possible. It appears that the respnse is associated with T-cell infiltration of the tumor, and transfer of tumor-infiltrating lymphocytes expanded in tissue culture with interleukin 2 is associated with significant antitumor effects. Further expansion of cultured human melanoma tumor-infiltrating lymphocytes with suppression of lymphokine-activated killer activity as well as the modulation of monocyte activity by interleukin 4 suggests that this cytokine may be clinically useful alone or in combination with interleukin 2. Other means of enhancing the activity of interleukin 2-based immunotheraphy are suggested by the finding that tumor cell susceptibility to lysis by natural killer cells is depressed following treatment with interferon γ and tumor necrosis factor, but susceptibility to lysis by tumor-infiltrating lymphocytes is markedly enhanced. Further development of these therapies will require innovative interpretation and application of findings related to the processing and presentation of human tumor antigens and the nature of tumor antigens and careful analysis of they T-cell receptor in antitumor effectors.