5-Fluorouracil and Interleukin-2 Immunochemotherapy Enhances Immunogenicity of Non-Small Cell Lung Cancer A549 Cells through Upregulation of NKG2D Ligands

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms ofimmunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC)A549 cells. Materials and
Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumorgrowth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cellswas evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) inA549 cells in vitro were also assessed.
Results: In A549-bearing nude mice, combination therapy significantlyinhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognitionand lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role inthe anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapysynergistically stimulated the expression and promoter activity of MICA/MICB.
Conclusions: 5-FU and IL-2immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and theseeffects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FUand IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhancedthe recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2may provide a new treatment option for patients with lung cancer