Introduction
Accumulating evidence alludes to a role for IL-11 signalling in tumour development although the mechanisms underlying IL-11 biology in tumourigenesis remain largely unknown. We postulate that IL-11 could be a mode of immunosuppression that can be targeted to mount an effective, immune-mediated anti-tumour response. Here we present data indicating IL-11 signalling drives tumour growth. Moreover, we identify an unrecognised immunological role for IL-11 in modulating T cell anti-tumour activity. Collectively, these findings validate IL-11 as a viable therapeutic strategy.
Method
To assess the therapeutic potential for targeting IL-11 signaling during tumourigenesis, colon and breast cancer cell lines were established in WT and Il11r-/- C57BL/6 mice. Mice were euthanised and the harvested tumours were immune profiled by FACs. To ascertain a role for IL-11 signalling in T cell activity, CD8+ T cells were FACs-sorted from WT and il11r-/- mice, and activated with PMA/ionomycin for 4h. T cell activation was assessed by measuring mRNA and protein levels of activation markers/cytokines by qPCR and ELISA, respectively.
Results
Colon and breast cancer growth was significantly attenuated in il11r-/- mice compared to WT hosts. Tumours from il11r-/- mice harboured higher numbers of activated T cells. Ex vivo T cell activation assays indicated that il11r-/- T cells also displayed heightened activation and cytolytic potential compared to their WT counterparts.
Conclusion
Here we report that IL-11 signalling supports tumourigenesis using various in vivo allograft mouse models. For the first time, we have characterised a functional role for IL-11 in modulating T cell function. Overall, the findings from this study indicate IL-11 signalling as a potential therapeutic target for the treatment of malignancies.