SUSCEPTIBILITY TO NK AND LAK CELLS IN MULTIDRUG RESISTANT SMALL CELL LUNG CARCINOMA

The sensitivity of tumour cells to lysis by natural killer (NK) and lymphocyte-activated killer (LAK) cells was studied in multidrug resistant (MDR) small cell lung carcinoma (SCLC) by both 51chromium release and by conjugate formation assays. The following observations were made: P-glycoprotein positive (P-gp+) MDR SCLC cell line variants were lysed by human LAK cells to a greater extent than were their drug sensitive counterparts. In contrast, a P-gp MDR SCLC cell line variants did not exhibit an increased susceptibility to LAK cells. Differential LAK susceptibility is not due to a generalized increase in target fragility to cellular immune system, because natural killer (NK) sensitivity has not been increased. Experiments designed to determine the mechanism of the effect indicated that there was not an artifactual increase in spontaneous release of 51Cr from the cells. Moreover, the P-gp+ MDR SCLC cells showed higher frequency of tumour cell binding to LAK cells than did the drug-sensitive parental line. It is proposed here that increased P-gp expression on SCLC tumour cell surface membranes gives the tumour cell an advantage in resistance against various drugs, but at the same time, this, or other associated membrane changes, puts the cell at a disadvantage by increasing the cell's susceptibility to LAK cell-mediated binding and lysis. These observations may lead to new insights on.