Natural-killer cell-mediated cytotoxicity of blood-lymphocytes from patients with malignant mesothelioma treated by intrapleural interleukin-2.

The most impressive biological effect of recombinant Interleukin-2 (rIL-2) is the generation of nonspecific killer cells that have lytic activity for a variety of tumor cells. Numerous studies have shown that these non specific killer cells might be of NK cell lineage even though they are different from resident NK-cell. We have examined the kinetics of the NK cell-mediated cytotoxicity of blood lymphocytes in patients after intrapleural rIL-2 administered for the treatment of pleural cancer. Escalating doses of rIL-2 were administered by intrapleural route to treat 11 patients with malignant pleural effusions due to malignant pleural mesothelioma (4 stage I, 4 stage II, 2 stage III, 1 stage IV). Two patients received respectively 3 cycles and 2 cycles of treatment. Peripheral blood lymphocyte cytotoxicity was assessed by an in vitro, chromium release microcytotoxicity assay against K562 cell line. Preliminary results indicate: (i) an important and prolonged increase in the cytotoxic response of blood lymphocytes in all patients but one having a clinical response and (ii) a lack of cytotoxicity or a baseline cytotoxic response of blood lymphocytes in all patients but one with no clinical response. These results likely point out the significance of NK-activity in the IL-2-induced antitumoral response and the interest of this in vitro assay for screening patients for further cycles of treatment.