Anti-tumoral Effects of Recombinant Lactococcus lactis Strain Secreting IL-17A Cytokine

Abstract

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine produced by T_H17 cells that participates and contributes in host defense and autoimmune disease. We have recently reported antitumor properties of the probiotic strain of <i>Lactobacillus casei</i> BL23 in mice and T_H17 cells was shown to play an important role in this beneficial effect. In order to better understand the role of IL-17A in cancer, we constructed a recombinant strain of <i>Lactococcus lactis</i> producing this cytokine and we determined its biological activity in: (i) a bioassay test for the induction of IL-6 production by murine fibroblasts 3T3 L1 cells line and (ii) in a mouse allograft model of human papilloma virus (HPV)-induced cancer. Our data show that recombinant <i>L. lactis</i> produces and efficiently secretes biologically active IL-17A cytokine. Interestingly, ∼26% of mice intranasally treated with <i>L. lactis</i>-IL-17A and challenged with TC-1 cells remained tumor free over the experiment, in contrast to control mice treated with the wild type strain of <i>L. lactis</i> which developed 100% of aggressive tumors. In addition, the median size of the ∼74% tumor-bearing mice treated with recombinant <i>L. lactis</i>-IL-17A, was significantly lower than mice treated with <i>L. lactis</i>-wt. Altogether, our results demonstrate that intranasal administration with <i>L. lactis</i> secreting IL-17A results in a partial protection against TC-1-induced tumors in mice, confirming antitumor effects of this cytokine in our cancer model.