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

Intrinsic or acquired resistance to anticancer drugs necessitated the search for different treatment modalities. The sensitivity of tumor cells to lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells was studied in multidrug resistant (MDR) small cell lung carcinoma (SCLC) by (51)Chromium (Cr-51) release and 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, P-gp(-), multidrug resistance protein 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 parental line. These observations may lead to new insights on combining chemotherapy with immunotherapy.