A major obstacle in clinical oncology is that tumors eventually acquire resistance to therapy. The mechanism by which resistance arises is usually associated with changes made in tumor cells in response to the therapy, however, little is known about the effect of the host which may also contribute to tumor resistance. In this study we uncovered the possible role IL-1β has on tumor progression following Paclitaxel (PTX) chemotherapy. We found that plasma and spleen from PTX-treated mice exhibited elevated expression of IL-1β. Furthermore, plasma from PTX-treated mice induced tumor cell invasion, an effect which was abrogated by plasma from mice treated with PTX and Anakinra, an IL-1 receptor antagonist. Consequently, mice inoculated with Lewis lung carcinoma (LLC) cells pre-exposed to plasma from mice treated with the combined therapy survived longer than mice inoculated with tumor cells pre-exposed to plasma from mice treated with PTX or Anakinra monotherapy. We next determined whether treatment efficacy of PTX is enhanced by the combination of PTX and Anakinra using 4T1 breast cancer model in mice. Tumors treated with the combined therapy were significantly smaller than tumors treated with PTX or Anakinra monotherapy. Surprisingly, although the primary tumors were smaller, such mice succumb to metastasis earlier than any of the other groups. Furthermore, an increased number of M2-macrophages colonizing 4T1 primary tumors treated with PTX and Anakinra was observed when compared to their number in PTX treated tumors, indicating a possible pro-metastatic role of M2-macrophages in post treatment IL-1β deprived microenvironment. Parallel results were observed when LLC bearing IL-1β deficient mice, were treated with PTX. Taken together, these findings demonstrate that although treatment outcome, at the primary tumor level, is enhanced following blocking of host-induced IL-1β expression, yet at the metastatic level, it may serve as a double-edge sward and can lead to metastatic spread.
