General Thoracic Surgery Functional Interleukin 4 Receptor and Interleukin 2 Receptor Common Γ-chain on Human Non–small Cell Lung Cancers: Novel Targets for Immune Therapy

late B cells, IL-4 has been found to activate cytotoxic T cells, modulate macrophage function, and cause B-cell immunoglobulin class switching.1,2 Our results and the I nterleukin 4 (IL-4) is primarily a T-lymphocyte and mast cell–derived cytokine with a variety of biologic functions. Originally described for its ability to stimuObjective: The interleukin 4 receptor has been demonstrated on the surface of human non–small cell lung carcinoma cell lines and tumor specimens. Interleukin 4 causes G1-phase cell-cycle arrest of non–small cell lung cancer cell lines expressing the interleukin 4 receptor; the effect directly correlates with the expression of the interleukin 4 receptor and is seen within 48 hours after treatment. We examined signal transduction pathways used by the interleukin 4 receptor that may account for growth arrest of the cell line LUst but had no effect on another non–small cell lung cancer cell line, SK-MES-1. Methods: Western blot analysis was performed on both LUst and SK-MES-1 cell lines cultured in the presence of interleukin 4 (500 U/mL). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins. Results: Western blotting of the cell lines with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kd, 100-130 kd, and 65 kd) phosphoproteins seen only in the interleukin 4–treated LUst cell line and not observed in the SK-MES-1 cell lines. Immunoprecipitation and blotting of the LUst cell line with specific secondary antibodies demonstrated that the 140-kd phosphoprotein was the interleukin 4 receptor, the 130-kd phosphoprotein was Janus kinase 1, the 116-kd phosphoprotein was Janus kinase 3, and the 65-kd phosphoprotein was the interleukin 2 receptor γ-chain. Specific binding was not observed in the non–small cell lung cancer cell line SK-MES-1, suggesting that a functional interleukin receptor γchain was not present. Southern blotting with complementary DNA probes to interleukin 2 receptor γ-chain confirmed the absence of this receptor on cell line SK-MES-1. Conclusions: These results suggest that non–small cell lung cancer cells may express functional cytokine receptors, including the interleukin 2 receptor γ-chain commonly found in association with the lymphocyte interleukin 2 receptor. These receptors may be novel targets for directing cytokine-based immune therapy. (J Thorac Cardiovasc Surg 2000;119:10-20) Richard Essner, MD Young Huynh, BS Tung Nguyen, BS Donald L. Morton, MD Dave S. B. Hoon, PhD