Analysis of CD137 and CD137L expression in human primary tumor tissues

To assess the expression of CD137 and CD137L in human primary tumor tissues and their potential role in tumor immunity.

Expression of CD137 and CD137L was assessed by immunohistochemistry in frozen sections of 12 human normal tissues, 15 benign tumors of epithelial or mesenchymal origin (adenoma and leiomyoma), and 36 malignant tumors of epithelial origin (squamous cell carcinoma and adenocarcinoma). The expression of CD137L on 9 human tumor cell lines (3 hepatocarcinoma, 2 lung carcinoma, 2 colon carcinoma, 1 lymphoma, and 1 leukemia) was detected by reverse transcription polymerase chain reaction. To analyze the role of CD137L expressed on tumor cells, we co-cultured tumor cells expressing CD137L with activated T lymphocytes expressing CD137 or with Chinese hamster ovary cells expressing CD137 and then detected by ELISA the levels of cytokines (IL-8, IFN-gamma) secreted by tumor cells or activated T cells.

The expression of CD137 and CD137L was observed only in human benign (2/15, 3/15) or malignant tumors (15/36, 21/36), but not in normal tissues (0/12, 0/12). CD137 was expressed on the vessel walls within tumor tissues, whereas CD137L was expressed on tumor cells. The expression of CD137 and CD137L was more common in malignant tumors, especially in moderate or low-differentiated tumors. Furthermore, CD137L expression found on tumor cell lines was functional because the ligation of CD137L on lung squamous carcinoma cells L78 with CD137 on T cells induced IFN-gamma production by T cells, and ligation of CD137L on hepatocarcinoma cells HepG2.2.15 with CD137 triggered tumor cells to produce IL-8.

CD137 and CD137L are expressed in different human primary tumor tissues, suggesting that they may influence the progression of tumors.