Effects of interleukin-1 receptor antagonist and chemotherapy on host-tumor interactions in established melanoma

Interleukin-1 (IL-1) has been implicated in the vascular and immune suppressor cell responses that promote tumor progression. IL-1, however, has also been shown to inhibit tumor progression by promoting antitumor immune responses and by enhancing the activity of chemotherapy.

The effects of IL-1 receptor antagonist (IL-1Ra), alone and combined with temozolomide and docetaxel chemotherapy, were examined in vitro and in vivo against microscopic and macroscopic mouse B16 melanoma.

IL-1Ra did not demonstrate antitumor activity in vitro, alone or combined with chemotherapy. When administered in vivo at the time when B16 cells were inoculated, IL-1Ra inhibited tumor growth. It did not affect growth when administered after tumors had established and were macroscopic. IL-1Ra increased M1 macrophage polarization and reduced myeloid-derived suppressor cells in mice with macroscopic tumors. Regulatory T-cells, tumor vascularity, and tumor interstitial fluid pressure were not significantly altered. Pre-treatment but not concurrent treatment with IL-1Ra enhanced the antitumor activity of chemotherapy in vivo against macroscopic tumors. Whereas chemotherapy reduced myeloid suppressor cells systemically, chemotherapy increased markers of myeloid suppressor cells intratumorally. These effects were attenuated by pre-treatment with IL-1Ra.

The effects of IL-1 and chemotherapy in melanoma are complex. IL-1Ra modifies myeloid suppressor cell populations and may have a role with chemotherapy in the treatment of established melanoma.