The tumor infiltrating lymphocytes (TIL) of human pulmonary tumors represent both a failure of the immune system and an opportunity for the recruitment of an anti-tumor effector system. We have shown that TIL have impaired NK activity that may be due to a deficit in recycling capacity. We now propose to examine the nature of the cytolytic defect in TIL NK cells. We will determine the phase of the cytotoxic reaction (binding, programming for lysis, or killer cell independent lysis) that is impaired in TIL. The kinetics of cytotoxicity under non-recycling conditions will be determined and the production of NK cytotoxic factor (NKCF) will be tested. The possible involvement of suppressor cells in the development of cytotoxic cells will be tested by the admixture of TIL to PBL responding to IL-2. The suppression of the acquisition of Tac and transferrin receptor, and the function, will be measured. The augmentation of TIL NK activity by IL-2 wil studied. IL-2 treated TIL do develop cytotoxic activity and we will determine the optimal conditions (including the role of IL-1, prostaglandin synthesis inhibitors such as indomethancin, and gamma-IFN) for IL-2 induction of cytotoxicity. Patients will be treated with IL-2 or with IL-2 plus LAK cells prior to surgery for pulmonary malignancy. The TIL will be extracted from these tumors and the cytotoxic function and activation marker expression determined. Collectively, these studies may identify better means of using the lymphoid population that is already physically closest to the tumor cells. Restoration of immune function to these cells may result in better control of tumor growth or spread.
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