Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma

Intrinsic or acquired resistance to anticancer drugs necessitated the searc h for different treatment modalities. The sensitivity of tumor cells to lys is by natural killer (NK) and lymphokine-activated killer (LAK) cells was s tudied in multidrug resistant (MDR) small cell lung carcinoma (SCLC) by (51 )Chromium (Cr-51) release and conjugate formation assays. The following obs ervations were made: P-glycoprotein positive (P-gp(+)) MDR SCLC cell line v ariants were lysed by human LAK cells to a greater extent than were their d rug sensitive counterparts. In contrast, P-gp(-), multidrug resistance prot ein positive (MRP+) variants of the same line did not exhibit an increased susceptibility to LAK cells. Differential LAK susceptibility is not due to a generalized increase in target fragility to cellular immunity, because NK sensitivity was not increased. Moreover, the P-gp(+) MDR SCLC cells showed a higher frequency of binding to LAK cells than did the drug-sensitive par ental line. These observations may lead to new insights on combining chemot herapy with immunotherapy.