Enhancement of Lymphokine-Activated Killer Cell Cytotoxicity Implicated in the Increased Expression of Surface Adhesion Molecules on Tumor Cells Treated with Anticancer Agents

Abstract

We investigated mechanisms underlying lymphokine-activated killer (LAK) cell cytotoxicity in terms of intensity of expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) on Daudi and KATO-III cells treated with cis-diamminedichloroplatinum (II) (CDDP) and mitomycin-C (MMC). Enhancement (mean, 49.8%) of ICAM-1 or LFA-3 in mRNA and protein expression on treated tumor cells was found by flow cytometry, slot-blot RNA analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Increases in adhesion and cytotoxicity of LAK cells to treated tumor cells were 10.1% and 17.7%, respectively. Results suggested that increased ICAM-l or LFA-3 expression by low-dose CDDP or MMC binds LAK cells to tumor cells, helping to kill tumor cells. Thus, LAK cell therapy with anticancer agent pretreatment could be useful for treatment of cancer patients.