IL-6-transfected tumor cells modulate the status of CD8⁺ and CD4⁺ T cells to control tumor growth

IL-6 is a proinflammatory cytokine secreted by tumor cells and immune cells to affect the development of cancer. This study demonstrates the effects of tumor-derived IL-6 on the malignancy of tumor cells and tumor immunity. The tumor cell line, EG7, was transfected with a mammalian expression vector encoding the full length of murine IL-6 to mimic IL-6-secreting tumor cells. Two IL-6 transfectants with low and high IL-6 production were compared in vitro and in vivo. While the in vitro proliferation rates of both transfectants and the parental line were similar, high expression of IL-6 induced a significant reduction in tumor growth in vivo. Concomitantly, there was an increase in IFN-γ positive tumor-infiltrating lymphocytes and a decrease in the suppressive CD4+CD25+FoxP3+ population. These results demonstrate the direct effects of tumor-derived IL-6 on cancer development and the induction of tumor immunity.