Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity.

Almeida, Rafael Ribeiro; Vieira, Raquel de Souza; Castoldi, Angela; Terra, Fernanda Fernandes; Melo, Amanda Campelo L.; Canesso, Maria Cecília Campos; Lemos, Luísa; Cipelli, Marcella; Rana, Nisha; Hiyane, Meire Ioshie; Pearce, Erika L.; Martins, Flaviano dos Santos; Faria, Ana Maria Caetano de; Câmara, Niels Olsen Saraiva

Background: Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear.Methods: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice.Results: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-β gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice.Conclusions: Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.

British Journal of Cancer, 2020, Vol 123, Issue 4, p534

0007-0920

Academic Journal

10.1038/s41416-020-0915-6