IL-6 Receptor Antibody Preferentially Affects Tumors in the Repopulation Phase of Growth

Abstract

IL-6 increases tumorigenic potential of primary human cancer stem cells. The goal of our study was to determine if an IL-6 receptor antibody (Tocilizumab) has an impact on tumor growth. IACUC approval was obtained before starting the experiments. The HNSCC cell line UT-SCC-14 was used for all experiments. A MTT assay was used to establish any effect of tocilizumab on cell growth. The effect of tocilizumab on clonogenic survival was also assessed. In the first set of experiments, a four armed study looked at tumor volume of flank tumors treated with a sham antibody (sham), tocilizumab (TOC), radiation (RT), and tocilizumab + radiation (TOC + RT). In the second set of experiments, a three arm study looked at flow cytometry stained for aldehyde dehydrogenase (ALDH) and CD44 at day 22, 30, and 43 with TOC, RT, TOC + RT for ex-vivo flank tumors. There was no significant difference in clonogenic survival in TOC versus the control. There was also no correlation with increasing concentration of TOC. In experiment 1, the TOC + RT had significantly smaller tumor volumes compared to the RT alone group at days 25 and 37 while trended for smaller tumor volumes at days 29 and 32. In experiment 2, the TOC + RT had significantly smaller tumor volumes compared to the RT alone group at days 31 and 35. On flow cytometry, ALDH(+) CD44(-) population significantly increased during day 30 in the TOC + RT group compared to both the TOC alone and RT alone. IL-6 receptor antibody has no effect on in vitro cell survival but does impact in vivo repopulation with an increase in non-cancer stem cells. Further studies are necessary to validate improvement with chemotherapy.