Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma
Savas, B.; Kerr, P.E.; Ustun, H.; Cole, S.P.; Pross, H.F.
Anticancer Research 18(6a): 4355-4361
1998
ISSN/ISBN: 0250-7005 PMID: 9891492 Document Number: 490409
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 51Chromium (51Cr) 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.